kapitel 4: genetische grundlagen der...

26
Kapitel 4: Genetische Grundlagen der Kanzerogenese Aas T, Børresen AL, Geisler S et al. (1996) Specific p53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nature Med 2: 811814 Adjei AA (2001) Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst 93: 10621074 Agami R, Blandino G, Oren M et al. (1999) Interaction of c-Abl and p73 and their collaboration to induce apoptosis. Nature 399: 809813 Aguilar F, Hussain SP, Cerutti P (1993) Aflatoxin B1 induces the transversion of G to T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA 90: 85868590 Ahmadian MR (2002) Prospects for anti-RAS drugs. Br J Haematol 116: 511518 Ahmadian MR, Zor T, Vogt D et al. (1999) Guanosine triphosphatase stimulation of oncogenic Ras mutants. Proc Natl Acad Sci USA 96: 70657070 Ahnesorg P, Smith P, Jackson SP (2006) XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124: 301313 Almoguera C, Shibata D, Forrester K et al. (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53: 549554 Alonso A, Sasin J, Bottini N et al. (2004) Protein tyrosine phosphatases in the human genome. Cell 117: 699711 Alsanea O, Clark OH (2001) Familial thyroid cancer. Curr Opin Oncol 13: 4451 Al-Tassan N, Chmiel NH, Maynard J et al. (2002) Inherited variants of MYH associated with somatic G:CT:A mutations in colorectal tumors. Nature Genet. 30: 227232 Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38: 729739 Ananthaswamy HN, Loughlin SM, Cox P et al. (1997) Sunlight and skin cancer: inhibition of p53 mutations in UV- irradiated mouse skin by sunscreens. Nature Med 3: 510514 Anker P, Lyautey J, Lederrey C et al. (2001) Circulating nucleic acids in plasma or serum. Clin Chim Acta 313: 143146 Apperley JF, Gardembras M, Melo JV et al. (2002) Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 347: 481487 Armanios MY, Chen JJl, Cogan JD et al. (2007) Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 356: 13171326 Armstrong SA, Staunton JE Silverman LB et al. (2002) MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nature Genet 30: 4147 Avner P, Heard E (2001) X-chromosome inactivation: counting, choice and initiation. Nature Genet 2: 5967 Bahram F, von der Lehr N, Cetinkaya C et al.(2000) c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover. Blood 95: 21042110 Bailleul B, Surani MA, White S et al. (1990) Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter. Cell 62: 697708 Baker SJ, Preisinger AC, Jessup JM (1990) p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 50: 77177722 Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499506 Balmain A (2002) Cancer as a complex genetic trait: tumor susceptibility in humans and mouse models. Cell 108: 145152 Barbacid M (1987) ras genes. Ann Rev Biochem 56: 779827 Bar-Sagi D (2001) A Ras by any other name. Moll Cell Biol 21: 14411443 Bartek J, Lukas J (2001) Are all cancer genes equal? Nature 411:10011002 Bartkova J, Horejsi Z, Koed K et al. (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864870 Bartram CR (1996) Molecular genetic aspects of myelodysplastic syndromes. Semin Hematol 33: 139149 Bartram CR, de Klein A, Hagemeijer A et al. (1983) Translocation of c-abl oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306: 277280 Bassing CH, Swat W, Alt FW (2002) The mechanism and regulation of chromosomal V(D)J recombination. Cell 109: S45‒S55 Bates S, Phillips AC, Clark PA et al.(1998) p14 ARF links the tumor suppressors RB and p53. Nature 395: 124125 Baumann P, Cech TR (2001) Pot 1, the putative telomere end-binding protein in fission yeast and humans. Science 292: 11711175

Upload: vanduong

Post on 18-Sep-2018

216 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Kapitel 4: Genetische Grundlagen der Kanzerogenese

Aas T, Børresen AL, Geisler S et al. (1996) Specific p53 mutations are associated with de novo resistance to

doxorubicin in breast cancer patients. Nature Med 2: 811–814

Adjei AA (2001) Blocking oncogenic Ras signaling for cancer therapy. J Natl Cancer Inst 93: 1062–1074

Agami R, Blandino G, Oren M et al. (1999) Interaction of c-Abl and p73 and their collaboration to induce

apoptosis. Nature 399: 809–813

Aguilar F, Hussain SP, Cerutti P (1993) Aflatoxin B1 induces the transversion of G to T in codon 249 of the p53

tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA 90: 8586–8590

Ahmadian MR (2002) Prospects for anti-RAS drugs. Br J Haematol 116: 511–518

Ahmadian MR, Zor T, Vogt D et al. (1999) Guanosine triphosphatase stimulation of oncogenic Ras mutants. Proc

Natl Acad Sci USA 96: 7065–7070

Ahnesorg P, Smith P, Jackson SP (2006) XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA

nonhomologous end-joining. Cell 124: 301‒313

Almoguera C, Shibata D, Forrester K et al. (1988) Most human carcinomas of the exocrine pancreas contain

mutant c-K-ras genes. Cell 53: 549–554

Alonso A, Sasin J, Bottini N et al. (2004) Protein tyrosine phosphatases in the human genome. Cell 117: 699‒711

Alsanea O, Clark OH (2001) Familial thyroid cancer. Curr Opin Oncol 13: 44–51

Al-Tassan N, Chmiel NH, Maynard J et al. (2002) Inherited variants of MYH associated with somatic G:CT:A

mutations in colorectal tumors. Nature Genet. 30: 227‒232

Amiel J, Lyonnet S (2001) Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 38:

729–739

Ananthaswamy HN, Loughlin SM, Cox P et al. (1997) Sunlight and skin cancer: inhibition of p53 mutations in UV-

irradiated mouse skin by sunscreens. Nature Med 3: 510–514

Anker P, Lyautey J, Lederrey C et al. (2001) Circulating nucleic acids in plasma or serum. Clin Chim Acta 313:

143–146

Apperley JF, Gardembras M, Melo JV et al. (2002) Response to imatinib mesylate in patients with chronic

myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J

Med 347: 481–487

Armanios MY, Chen JJl, Cogan JD et al. (2007) Telomerase mutations in families with idiopathic pulmonary

fibrosis. N Engl J Med 356: 1317‒1326

Armstrong SA, Staunton JE Silverman LB et al. (2002) MLL translocations specify a distinct gene expression

profile that distinguishes a unique leukemia. Nature Genet 30: 41–47

Avner P, Heard E (2001) X-chromosome inactivation: counting, choice and initiation. Nature Genet 2: 59–67

Bahram F, von der Lehr N, Cetinkaya C et al.(2000) c-Myc hot spot mutations in lymphomas result in inefficient

ubiquitination and decreased proteasome-mediated turnover. Blood 95: 2104–2110

Bailleul B, Surani MA, White S et al. (1990) Skin hyperkeratosis and papilloma formation in transgenic mice

expressing a ras oncogene from a suprabasal keratin promoter. Cell 62: 697–708

Baker SJ, Preisinger AC, Jessup JM (1990) p53 gene mutations occur in combination with 17p allelic deletions as

late events in colorectal tumorigenesis. Cancer Res 50: 7717–7722

Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and

dimer dissociation. Nature 421: 499–506

Balmain A (2002) Cancer as a complex genetic trait: tumor susceptibility in humans and mouse models. Cell 108:

145–152

Barbacid M (1987) ras genes. Ann Rev Biochem 56: 779–827

Bar-Sagi D (2001) A Ras by any other name. Moll Cell Biol 21: 1441–1443

Bartek J, Lukas J (2001) Are all cancer genes equal? Nature 411:1001–1002

Bartkova J, Horejsi Z, Koed K et al. (2005) DNA damage response as a candidate anti-cancer barrier in early

human tumorigenesis. Nature 434: 864‒870

Bartram CR (1996) Molecular genetic aspects of myelodysplastic syndromes. Semin Hematol 33: 139–149

Bartram CR, de Klein A, Hagemeijer A et al. (1983) Translocation of c-abl oncogene correlates with the presence

of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306: 277–280

Bassing CH, Swat W, Alt FW (2002) The mechanism and regulation of chromosomal V(D)J recombination. Cell

109: S45‒S55

Bates S, Phillips AC, Clark PA et al.(1998) p14ARF links the tumor suppressors RB and p53. Nature 395: 124–125

Baumann P, Cech TR (2001) Pot 1, the putative telomere end-binding protein in fission yeast and humans.

Science 292: 1171–1175

Page 2: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Baylin SB, Herman JG, Graff JR et al. (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia.

Adv Cancer Res 72: 141–196

Bell, DW, Varley JM, Szydlo TE et al. (1999) Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

Science 286: 2528–2531

Bemark M, Neuberger MS (2000) The c-MYC allele that is translocated into the IgH locus undergoes constitutive

hypermutation in a Burkitt’s lymphoma line. Oncogene 19: 3404–3410

Bentires-Alj M, Kontaridis MI, Neel B. G (2006) Stops along the RAS pathway in human genetic disease. Nature

Med. 12: 283‒285

Berger SL (2002) Histone modifications in transcriptional regulation. Curr Opin Genet Dev 12: 142–148

Bergamashi D, Samuels Y, Sullivan A et al. (2006) iASPP preferentially finds P53 proline-rich region and

modulates apoptotic function of codon 72‒polymorphic p53. Nature Genet. 38: 1133‒1141

Bhattacharjee A, Richards WG, Staunton J et al. (2001) Classification of human lung carcinomas by mRNA

expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 98:13790–13795

Bielas JH, Loeb KR, Rubin BP et al. (2006) Human cancers express a mutator phenotype. Proc. Natl. Acad. Sci

(USA) 103: 18238‒18242

Bienvenu T, Chelly J. (2006) Molecular genetics of Rett syndrome: when methylation goes unrecognized. Nature

Rev. Genet. 7: 415‒426

Bird A (2001) Methylation talk between histones and DNA. Science 294: 2113–2115

Bird AP, Wolffe AP (1999) Methylation-induced repression – belts, braces, and chromatin. Cell 99:451–454

Bischoff JR, Kirn DH, Williams A et al. (1996) An adenovirus mutant that replicates selectively in p53-Deficient

human tumor cells. Science 274: 373–376

Bishop JM (1985) Viral oncogenes. Cell 42: 23–38

Bishop JM (1991) Molecular themes in oncogenesis. Cell 64: 235–248

Bittner M, Meltzer P, Chen Y et al. (2000) Molecular classification of cutaneous malignant melanoma by gene

expression profiling. Nature 406: 536–540

Blackburn EH (2001) Switching and signaling at the telomere. Cell 106: 661–673

Blanco JG, Dervieux T, Edick MJ et al. (2001) Molecular emergence of acute myeloid leukemia during treatment

for acute lymphoblastic leukemia. Proc Natl Acad Sci USA 98: 10338–10343

Blander G, Kipnis J, Leal JFM et al. (1999) Physical and functional interaction between p53 and the Werner’s

syndrome protein. J Biol Chem 274: 29463–29469

Blasco MA (2005) Telomeres and human disease: ageing, cancer and beyond. Nature Rev. Genet. 6: 611‒622

Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126: 37‒47

Blunt T, Finnie NJ, Taccioli GE et al. (1995) Defective DNA-dependent protein kinase activity is linked to V(D)J

recombination and DNA repair defects associated with the murine scid mutation. Cell 80: 813–823

Bochar DA, Wang L, Beniya H et al. (2000) BRCA1 is associated with a human SWI/SNF-related complex: linking

chromatin remodeling to breast cancer. Cell 102: 257–265

Bogenhagen DF (1999) Repair of mtDNA in vertebrates. Am J Hum Genet 64: 1276–1281

Boguski MS, McCormick F (1993) Proteins regulating Ras and its relatives. Nature 366: 643–654

Bollag G, Clapp DW, Shih S et al. (1996) Loss of NF1 results in activation of the Ras signaling pathway and leads

to aberrant growth in haematopoietic cells. Nature Genet 12: 144–148

Bongarzone I, Butti MG, Coronelli S et al. (1994) Frequent activation of ret protooncogene by fusion with a new

activating gene in papillary thyroid carcinomas. Cancer Res 54: 2979–2985

Bos JL (1989) ras oncogenes in human cancer: a review. Cancer Res 49: 4682–4689

Bos JL (1998) All in the family? New insights and questions regarding interconnectivity of Ras, Rap 1 and Ral.

EMBO J 17: 6776–6782

Bos JL, Fearon ER, Hamilton SR et al. (1987) Prevalence of ras gene mutations in human colorectal cancers.

Nature 327: 293–297

Botstein D, White RL, Skolnick M et al. (1980) Construction of a genetic linkage map in man using restriction

fragment length polymorphisms. Am J Hum Genet 32: 314–331

Bouchard C, Staller P, Eilers M (1998) Control of cell proliferation by Myc. Trends Cell Biol 8: 202–206

Boveri T (1914) Zur Frage der Entstehung maligner Tumoren. Gustav Fischer, Jena

Box NF, Duffy DL, Chen W et al. (2001) MC1R genotype modifies risk of melanoma in families segregating

CDKN2A mutations. Am J Hum Genet 69: 765–773

Boxer LM, Dang CV (2001) Translocations involving c-myc and c-myc function. Oncogene 20: 5595–5610

Boxer RB, Jang JW, Sintasath L et al. (2004) Lack of sustained repression of c-MYC-induced mammary

adenocarcinomas following brief or prolonged MYC inactivation. Cancer Cell 6: 577‒586

Boyd SD, Tsai KY, Jacks T (2000) An intact HDM 2 RING-finger domain is required for nuclear exclusion of p53.

Nature Cell Biol 2: 563–568

Page 3: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Bradshaw PS, Stavropoulos DJ, Meyn MS (2005) Human telomeric protein TRF2 associates with genomic

double-strand breaks as an early response to DNA damage. Nature Genet. 37: 193‒197

Brandon M, Baldi P, Wallace DC (2006) Mitochondrial mutations in cancer. Oncogene 25: 4647‒4662

Brash DE, Rudolph JA, Simon JA et al. (1991) A role for sunlight in skin cancer: UV-induced p53 mutations in

squamous cell carcinoma. Proc Natl Acad Sci USA 88: 10124–10128

Braunger J, Schleithoff L, Schulz AA et al.(1997) Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is

mediated mainly by a multi-substrate docking-site. Oncogene 14: 2619–2631

Breit TM, Beishuizen A, Ludwig WD et al. (1993) tal-1 deletions in T-cell acute lymphoblastic leukemia as PCR

target for detection of minimal residual disease. Leukemia 7: 2004–2011

Brison O (1993) Gene amplification and tumor progression. Biochim Biophys Acta 1155: 25–41

Brown J, Saracoglu K, Uhrig S et al. (2001) Subtelomeric chromosome rearrangements are detected using an

innovative 12‒color FISH assay (M-TEL). Nature Med 7: 497–501

Brown L, Cheng JT, Chen Q et al. (1990) Site-specific recombination of the tal-1 gene is a common occurrence in

human T cell leukemia. EMBO J 9: 3343–3351

Bruder CEG, Piotrowski A, Gijsbers AACG et al. (2008) Phenotypically concordant and discordant monozygotic

twins display different DNA copy-number-variation profiles. Am. J. Hum. Genet. 82: 763‒771

Brummelkamp TR, Bernards R, Agami R (2002) Stable suppression of tumorigenicity by virus-mediated RNA

interference. Cancer Cell 2: 243–247

Bryan TM, Englezou A, Dalla-Pozza L et al. (1997) Evidence for an alternative mechanism for maintaining

telomere length in human tumors and tumor-derived cell lines. Nature Med 3: 1271–1274

Brzovic PS, Rajagopal P, Hoyt DW et al. (2001) Structure of a BRCA1‒BARD1 heterodimeric RING-RING

complex. Nature Struct Biol 8: 833–837

Bueno MJ, de Castro IP, de Cedron MG et al. (2008) Genetic and epigenetic silencing of microRNA-203

enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 13: 496‒506

Bulavin DV, Demidov ON, Saito S et al. (2002) Amplification of PPM1D in human tumors abrogates p53 tumor-

suppressor activity. Nature Genet 31: 210–215

Bunz F, Dutriaux A, Lengauer C et al. (1998) Requirement for p53 and p21 to sustain G2 arrest after DNA

damage. Science 282: 1497–1501

Buschmann T, Fuchs SY, Lee CG et al. (2000) SUMO-1 modification of Mdm2 prevents its self-ubiquitination and

increases Mdm2 ability to ubiquitinate p53. Cell 101: 753–762

Bykov VJN, Issaeva N, Shilov A (2002) Restoration of the tumor suppressor function to mutant p53 by a low-

molecular-weight compound. Nature Med 8: 282–288

Byrne JL, Marshall CJ (1998) The molecular pathophysiology of myeloid leukemias: Ras revisited. Br J Haematol

100: 256–264

Cáceres JF, Kornblihtt AR (2002) Alternative splicing: multiple control mechanisms and involvement in human

disease. Trends Genet 18: 186–193

Cahill DP, Lengauer C, Yu J et al. (1998) Mutations of mitotic checkpoint genes in human cancers. Nature 392:

300–303

Calin GA, Croce CM (2007) Chromosomal rearrangements and microRNAs: a new cancer link with clinical

implications. J. Clin. Invest. 117: 2059‒2066

Call KM, Glaser T, Ito CY et al. (1990) Isolation and characterization of a zinc finger polypeptide gene at the

human chromosome 11 Wilms’tumor locus. Cell 60: 509–520

Canman CE, Lim DA, Cimprich KA et al. (1998) Activation of the ATM kinase by ionizing radiation and

phosphorylation of p53. Science 281: 1677–1679

Cannon-Albright LA, Skolnick MH, Bishop DT et al. (1988) Common inheritance of susceptibility to colonic

adenomatous polyps and associated colorectal cancers. N Engl J Med 319: 533–537

Cao L, Finkel T (2006) Cancer gets the Chk’ered flag. Nature Med. 12: 1354‒1356

Carlomagno F, Salvatore G, Cirafici AM et al. (1997) The different RET-activating capability of mutations of

cysteine 620 or cysteine 634 correlates with the multiple endocrine neoplasia type 2 disease phenotype.

Cancer Res 57: 391–395

Carlson BA, Dubay MM, Sausville EA et al. (1996) Flavopiridol induces G1 arrest with inhibition of cyclin-

dependent kinase (CDK) 2 and CDK4 in human breast carcinoma cells. Cancer Res 56: 2973–2978

Carlson B, Lahusen T, Singh S et al. (1999) Down-regulation of cyclin D1 by transcriptional repression in MCF-7

human breast carcinoma cells induced by flavopiridol. Cancer Res 59: 4634–4641

Carnero A, Hudson JD, Price CM et al. (2000) p16INK4a and p19ARF act in overlapping pathways in cellular

immortalization. Nature Cell Biol 2: 148–155

Cassidy SB, Dykens E, Williams CA (2000) Prader-Willi and Angelman syndromes: sister imprinted disorders. Am

J Med Genet 97: 136–146

Page 4: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Cavé H, van der Werff ten Bosch J, Suciu S et al. (1998) Clinical significance of minimal residual disease in

childhood acute lymphoblastic leukemia. N Engl J Med 339: 591–598

Cayuela JM, Gardie B, Sigaux F (1997) Disruption of the multiple tumor suppressor gene

MTS1/p16INK4a/CDKN2 by illegitimate V(D)J recombinase activity in T-cell acute lymphoblastic leukemias.

Blood 90: 3720–3726

Chaganti RSK, Schonberg S, German J (1974) A manyfold increase in sister chromatid exchanges in Bloom’s

syndrome lymphocytes. Proc Natl Acad Sci USA 71: 4508–4512

Chan AT, Ogino S, Fuchs CS (2007) Aspirin and the risk of colorectal cancer in relation to the expression of COX-

2. N. Engl. J. Med. 356: 2131‒2142

Chan TA, Hermeking H, Lengauer C et al. (1999) 14–3–3is required to prevent mitotic catastrophe after DNA

damage. Nature 401: 616–620

Chan TL, Yuen ST, Kong CK et al. (2006) Heritable germline epimutation of MSH2 in a family with hereditary

nonpolyposis colorectal cancer. Nature Genet. 38: 1178‒1183

Chang TC, Yu D, Lee YS et al. (2008) Widespread micro RNA expression by MYC contributes to tumorigenesis.

Nature Genet. 40: 43‒50

Chatterjee A, Mambo E, Sidransky S (2006) Mitochondrial DNA mutations in human cancer. Oncogene 25:

4663‒4674

Chellappan SP, Hiebert S, Mudryi M et al. (1991) The E2F transcription factor is a cellular target for the RB

protein. Cell 65: 1053–1061

Chen HL, Carbone DP (1997) p53 as a target for anti-cancer immunotherapy. Mol Med Today 4: 160–167

Chen X (1999) The p53 family: same response, different signals? Mol Med Today 5: 387–392

Chen YNP, Sharma SK, Ramsey TM et al. (1999) Selective killing of transformed cells by cyclin/cyclin-dependent

kinase 2 antagonists. Proc Natl Acad Sci USA 96: 4325–4329

Chen YQ, Hsieh JT, Yao F et al. (1999) Induction of apoptosis and G2/M cell cycle arrest by DDC. Oncogene 18:

2747–2754

Chen Z, Trotman LC, Shaffer D et al. (2005) Crucial role of p53-Dependent cellular senescence in suppression of

Pten-deficient tumorigenesis. Nature 436: 725‒730

Chin L, Pomerantz J, DePinho RA (1998) The INK4a/ARF tumor suppressor: one gene – two products – two

pathways. TIBS 23: 291–296

Chin L, Tam A, Pomerantz J et al. (1999) Essential role for oncogenic Ras in tumour maintenance. Nature 400:

468–471

Chinnery PF, Turnbull DM (2000) Mitochondrial DNA mutations in the pathogenesis of human disease. Mol Med

Today 6: 425–431

Cho KR, Oliver JD, Simons JW et al. (1994) The DDC gene:structural analysis and mutations in colorectal

carcinomas. Genomics 19, 525–531

Choy E, Chiu VK, Silletti J et al. (1999) Endomembrane trafficking of Ras: the CAAX motif targets proteins to the

Er and Golgi. Cell 98: 69–80

Christofk HR, Vander Heiden MG, Wu N et al. (2008a) Pyruvate kinase M2 is a phosphotyrosine-binding protein.

Nature 452: 181‒186

Christofk HR, Vander Heiden MG, Harris MH et al. (2008b) The M2 splice isoform of pyruvate kinase is important

for cancer metabolism and tumour growth. Nature 452: 230‒233

Cimmino A, Calin GA, Fabbri M et al. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl.

Acad. Sci. (USA) 102: 13944‒13949

Citterio E, Vermeulen W, Hoeijmakers JHJ (2000) Transcriptional healing. Cell 101: 447–450

Cloos PAC, Christensen J, Agger K et al. (2006) The putative oncogene GASC1 demethylates tri- and

dimethylated lysine 9 on histone H3. Nature 442: 307‒311

Coffey MC, Strong JE, Forsyth PS et al. (1998) Reovirus therapy of tumors with activated Ras pathway. Science

282: 1332–1334

Cohn SL (1999) Diagnosis and classification of the small round-cell tumors of childhood. Am J Pathol 155: 11–15

Colaluca IN, Tosoni D, Nuciforo P et al. (2008) NUMB controls p53 tumour suppressor activity. Nature 451: 76‒80

Coller HA, Khrapko K, Bodyak ND et al. (2001) High frequency of homoplasmic mitochondrial DNA mutations in

human tumors can be explained without selection. Nature Genet 28: 147–150

Comings DE (1973) A general theory of carcinogenesis. Proc Natl Acad Sci USA 70: 3324–3328

Conacci-Sorrell M, Zhurinsky J, Ben-Ze’ev A (2002) The cadherin-catenin adhesion system in signaling and

cancer. J Clin Invest 109: 987–991

Contente A, Dittmer A, Koch MC et al. (2002) A polymorphic microsatellite that mediates induction of PIG3 by

p53. Nature Genet 30: 315–320

Coppes MJ, Haber DA, Grundy PE (1994) Genetic events in the development of Wilms’tumor. N Engl J Med 331:

586–590

Page 5: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Cordenonsi M, Montagner M, Adorno M et al. (2007) Integration of TGF- β and RAS/MAPK signaling through p53

phosphorylation. Science 315: 840‒843

Cordon-Cardo C (1995) Mutation of cell cycle regulators: biological and clinical implications for human neoplasia.

Am J Pathol 147: 545–560

Cortez D, Elledge SJ (2000) Conducting the mitotic symphony. Nature 406: 354–356

Costello JF, Vertino PM (2002) Methylation matters: a new spin on maspin. Nature Genet 31: 123–126

Courtois-Cox S, Williams SMG, Reczek EE et al. (2006) A negative feedback signaling network underlies

oncogene-induced senescence. Cancer Cell 10: 459‒472

Cui H, Horon IL, Ohlsson R et al. (1998) Loss of imprinting in normal tissue of colorectal cancer patients with

microsatellite instability. Nature Med 4: 1276–1279

Cui R, Widlund HR, Feige E et al. (2007) Central role of P53 in the suntan response and pathologic

hyperpigmentation. Cell 128: 853‒864

Cunningham JM, Christensen ER, Tester DJ et al. (1998) Hypermethylation of the hMLH1 promoter in colon

cancer with microsatellite instability. Cancer Res 58: 3455–3460

Cuthbert AP, Fisher SA, Mirza MM et al. (2002) The contribution of NOD2 gene mutations to the risk and site of

disease in inflammatory bowel disease. Gastroenterology 122: 867–874

D’Adda di Fugagna (2008) Living on break: cellular senescence as a DNA-damage response. Nature Rev.

Cancer 8: 512‒522

Dai Y, Kysela B, Hanakahi LA et al. (2003) Nonhomologous end joining and V(D)J recombination require an

additional factor. Proc. Natl. Acad. Sci. (USA) 100: 2462‒2467

Damm K, Hemmann U, Garin-Chesa P et al.(2001) A highly selective telomerase inhibitor limiting human cancer

cell proliferation. EMBO J 20: 6958–6968

Danaei G, vander Hoorn S, Lopez AD et al. (2005) Causes of cancer in the world: comparative risk assessment of

nine behavioural and environmental risk factors. Lancet 366: 1784‒1793

Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19: 1–11

Danckwardt S, Hentze MW, Kulozik AE (2008) 3’ end mRNA processing: molecular mechanisms and implications

for health and disease. EMBOJ 27: 482‒498

Davies H, Bignell GR, Cox C et al. (2002) Mutations of the BRAF gene in human cancer. Nature 417: 949‒954

D’Cruz CM, Gunther EJ, Boxer RB et al. (2001) c-MYC induces mammary tumorigenesis by means of a preferred

pathway involving spontaneous Kras2 mutations. Nature Med 7: 235–239

de la Chapelle A (2004) Genetic predisposition to colorectal cancer. Nature Rev. Cancer 4: 769‒780

De Azevedo WF, Mueller-Dieckmann HJ, Schulze-Gahmen U et al. (1996) Structural basis for specificity and

potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc Natl Acad Sci USA 93: 2735–2740

de Klein A, van Kessel AG, Grosveld G et al. (1982) A cellular oncogene is translocated to the Philadelphia

chromosome in chronic myelocytic leukaemia. Nature 300: 765–767

DeBaun MR, Niemitz EL, McNeil DE et al. (2002) Epigenetic alterations of H19 and LIT1 distinguish patients with

Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet 70: 604–611

Deininger MWN, Goldman JM, Melo JV (2000a) The molecular biology of chronic myeloid leukemia. Blood 96:

3343–3356

Deininger MWN, Vieira S, Mendiola R et al. (2000b) BCR-ABL tyrosine kinase activity regulates the expression of

multiple genes implicated in the pathogenesis of chronic myeloid leukemia. Cancer Res 60:2049–2055

Delattre O, Zucman J, Melot T et al. (1994) The Ewing family of tumors – a subgroup of small-round-cell tumors

defined by specific chimeric transcripts. N Engl J Med 331: 294–299

Demetri GD, von Mehren M, Blanke CD et al. (2002) Efficacy and safety of imatinib mesylate in advanced

gastrointestinal stromal tumors. N Engl J Med 347: 472–480

Denissenko MF, Pao A, Tang M et al. (1996) Preferential formation of benzo[a]pyrene adducts at lung cancer

mutational hotspots in p53. Science 274: 430–432

Desai KV, Xiao N, Wang W et al. (2002) Initiating oncogenic event determines gene-expression patterns of

human breast cancer models. Proc Natl Acad Sci USA 99: 6967–6972

Devilee P (1999) BRCA1 and BRCA2 testing: weighing the demand against the benefits. Am J Hum Genet 64:

943–948

DiCiommo D, Gallie BL, Bremner R (2000) Retinoblastoma: the disease, gene and protein provide critical leads to

understand cancer. Sem Cancer Biol 10: 255–269

Di Croce L, Raker VA, Corsaro M et al. (2002) Methyltransferase recruitment and DNA hypermethylation of target

promoters by an oncogenic transcription factor. Science 295: 1079–1082

Dik WA, Nadel B, Przybylski Gk et al. (2007) Different chromosomal breakpoints impact the level of LMO2

expression in T-ALL. Blood 110: 388‒392

Diehl F, Schmidt K, Choti MA (2008) Circulating mutant DNA to assess tumor dynamics. Nature Med. 14:

985‒990

Page 6: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Dominguez-Sola D, Ying CY, Grandori C et al. (2007) Non-transcriptional control of DNA replication by c-MYC.

Nature 448: 445‒451

Dong DL, Liu R, Sherlock R et al. (1999) Molecular forceps from combinatorial libraries prevent the farnesylation

of Ras by binding to its carboxyl terminus. Chem Biol 6: 133–141

Dornan D, Wertz I, Shimizu H et al. (2004) The ubiquitin ligase COP1 is a critical negative regulator of P53.

Nature 429: 86‒92

Downward J (2003) Targeting RAS signalling pathways in cancer therapy. Nature Rev Cancer 3: 11–22

Drews J (2000) Drug discovery: a historical perspective. Science 287: 1960–1964

Druker BJ (2002) Perspectives on the development of a molecularly targeted agent. Cancer Cell 1: 31–36

Druker BJ, Sawyers CL, Kantarjian H et al. (2001a) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase

in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia

chromosome. N Engl J Med 344: 1038–1042

Druker BJ, Talpaz M, Resta DJ et al. (2001b) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine

kinase in chronic myeloid leukemia. N Engl J Med 344: 1031–1037

Dunham MA, Neumann AA, Fasching LC et al. (2000) Telomere maintenance by recombination in human cells.

Nature Genet 26: 447–450

Duval A, Hamelin R (2002) Mutations at coding repeat sequences in mismatch repair-deficient human cancers:

toward a new concept of target genes for instability. Cancer Res 62: 2447–2454

Duval A, Gayet J, Zhou XP et al. (1999) Frequent frameship mutations of the TCF-4 gene in colorectal cancers

with microsatellite instability. Cancer Res 59: 4213–4215

Duval A, Rolland S, Compoint A et al. (2001) Evolution of instability at coding and non-coding repeat sequences

in human MSI-H colorectal cancers. Hum Mol Genet 10: 513–518

Early Breast Cancer Trialists’ Collaborative Group (1998 a) Tamoxifen for early breast cancer: an overview of the

randomized trials. Lancet 351: 1451–1467

Early Breast Cancer Trialists’ Collaborative Group (1998b) Polychemotherapy for early breast cancer: an

overview of the randomized trials. Lancet 352: 930–942

Eberhart CE, Coffey RJ, Radhika A et al. (1994) Up-regulation of cyclooxygenase 2 gene expression in human

colorectal adenomas and adenocarcinomas. Gastroenterology 107: 1183–1188

Edgen H, Kallioniemi O (2006) Integrated breast cancer genomics. Cancer Cell 10: 453‒454

Egan SE, Giddings BW, Brooks MW et al. (1993) Association of Sos Ras exchange protein with Grb2 is

implicated in tyrosine kinase signal transduction and transformation. Nature 363: 45–51

El-Deiry WS (1998) Regulation of p53 downstream genes. Sem Cancer Biol 8: 345–357

Ellis CN, Ellis MB, Blakemore WS (1987) Effect of adriamycin on heart mitochondrial DNA. Biochem J 245: 309–

312

Ellis NA, Groden J, Ye ZH et al. (1995) The Bloom’s syndrome gene product is homologous to RecQ helicases.

Cell 83: 655–666

Enard W, Khaitovich P, Klose J et al. (2002) Intra- and interspecific variation in primate gene expression patterns.

Science 296: 340–343

Eng C (1996) The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung’s disease. N

Engl J Med 335: 943–951

Epel ES, Blackburn EH, Lin J et al. (2004) Accelerated telomere shortening in response to life stress. Proc. Natl.

Acad. Sci. (USA) 101: 17312‒17315

Eppert K, Scherer SW, Ozcelik H et al. (1996) MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-

related protein that is functionally mutated in colorectal carcinoma. Cell 86: 543–552

Epstein CJ, Martin GM, Schultz AL et al. (1966) Werner’s syndrome: a review of its symptomatology, natural

history, pathologic features, genetics and relationship to the natural aging process. Medicine 45: 177–221

Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nature Rev. Genet. 8:

286‒298

Esteller M, Catasus L, Matias-Guiu X et al. (1999) hMLH1 promoter hypermethylation is an early event in human

endometrial tumorgenesis. Am J Pathol. 155: 1767–1771

Esteller M, Silva JM, Dominguez G et al. (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic

breast and ovarian tumors. J Natl Cancer Inst 92: 564–569

Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics.

Science 286: 487–491

Falck J, Mailand N, Syljuåsen RG et al. (2001) The ATM-Chk2‒Cdc25A checkpoint pathway guards against

radioresistant DNA synthesis. Nature 410: 842–847

Fan C, Oh DS, Wessels L et al. (2006) Concordance among gene-expression –based predictors for breast

cancer. N. Engl. J. Med. 355: 560‒569

Page 7: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Fantl WJ, Johnson DE, Williams LT (1993) Signalling by receptor tyrosine kinases. Annu Rev Biochem 62: 453–

481

Fasano O, Birnbaum D, Edlund L et al. (1984) New human transforming genes detected by a tumorigenicity

assay. Mol Cell Biol 4: 1695–1705

Feinberg AP (2000) The two-domain hypothesis in Beckwith-Wiedemann syndrome. J Clin Invest 106: 739–740

Feinberg AP (2001) Cancer epigenetics takes center stage. Proc Natl Acad Sci USA 98: 392–394

Felsher DW, Bishop JM (1999) Reversible tumorgenesis by MYC in hematopoietic lineages. Mol Cell 4: 199–207

Feraon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759–767

Ferguson DO, Alt FW (2001) DNA double strand break repair and chromosomal translocation: lessons from

animal models. Oncogene 20: 5572–5579

Fero ML, Randel E, Gurley KE et al. (1998) The murine gene p27Kip1 is haploinsufficient for tumour suppression.

Nature 396: 177–180

Ferrando AA, Neuberg DS, Staunton J et al. (2002) Gene expression signatures define novel oncogenic

pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1: 75–87

Finak G, Bertas N, Pepin F et al. (2008) Stromal gene expression predicts clinical outcome in breast cancer.

Nature Med. 14: 518‒527

Finette BA, Poseno T, Albertini RJ (1996) V(D)J recombinase-mediated HPRT mutations in peripheral blood

lymphocytes of normal children. Cancer Res 56: 1405–1412

Finlay CA, Hinds PW, Levine AJ (1989) The p53 proto-oncogene can act as a suppressor of transformation. Cell

57: 1083–1093

Fischle W, Tseng BS, Dormann HL et al. (2005) Regulation of HP1‒chromatin binding by histone H3 methylation

and phosphorylation. Nature 438: 1116‒1122

Fishel R (2001) The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising

the mutator hypothesis. Cancer Res 61: 7369–7374

Fishel R, Kolodner RD (1995) Identification of mismatch repair genes and their role in the development of cancer.

Curr Opin Genet Dev 5: 382–395

Fisher GH, Wellen SL, Klimstra D et al. (2001) Induction and apoptotic regression of lung adenocarcinomas by

regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev 15:

3249–3262

Fliss MS, Usadel H, Caballero OL et al. (2000) Facile detection of mitochondrial DNA mutations in tumors and

bodily fluids. Science 287: 2017–2019

Flohr T, Schrauder A, Cazzaniga G et al. (2008) Minimal residual disease (MRD)-directed risk stratification using

real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the

international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia (ALL).

Leukemia (in press)

Flores ER, Tsai KY, Crowley D et al. (2002) p63 and p73 are required for p53-Dependent apoptosis in response

to DNA damage. Nature 416: 560–564

Forastiere A, Koch W, Trotti A et al. (2001) Head and neck cancer. N Engl J Med 345: 1890–1900

Foster BA, Coffey HA, Morin MJ et al. (1999) Pharmacological rescue of mutant p53 conformation and function.

Science 286: 2507–2510

Fraga MF, Ballestar E, Paz MF et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins.

Proc. Natl. Acad. Sci. (USA) 102: 10604‒10609

Franchitto A, Pichierri P (2002) Protecting genomic integrity during DNA replication: correlation between Werner’s

and Bloom’s syndrome gene products and the MRE11 complex. Hum Mol Genet 11: 2447–2453

Friedler A, Hansson LO, Veprintsev DB et al.(2002) A peptide that binds and stabilizes p53 core domain:

chaperone strategy for rescue of oncogenic mutants. Proc Natl Acad Sci USA 99: 937–942

Friend SH, Bernards R, Rogelj S et al. (1986) A human DNA segment with properties of the gene that

predisposes to retinoblastoma and osteosarcoma. Nature 323: 643–646

Frigola J, Song J, Stirzaker C et al. (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene

suppression across an entire chromosome band. Nature Genet. 38: 540‒549

Frizelle SP, Grim J, Zhou J et al. (1998) Re-expression of p16INK4a in mesothelioma cells results in cell cycle

arrest, cell death, tumor suppression and tumor regression. Oncogene 16: 3087–3095

Futaki M, Liu JM (2001) Chromosomal breakage syndromes and the BRCA1 genome surveillance complex.

Trends Mol Med 7: 560–565

Futreal PA, Coin L, Marshall M et al. (2004) A consensus of human cancer genes. Nature Rev. Cancer 4:

177‒183

Gabriel SB, Salomon R, Pelet A et al. (2002) Segregation at three loci explains familial and population risk in

Hirschsprung’s disease. Nature Genet 31: 89–93

Page 8: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Gale KB, Ford AM, Repp R et al.(1997) Backtracking leukemia to birth: identification of clonotypic gene fusion

sequences in neonatal blood spots. Proc Natl Acad Sci USA 94: 13950–13954

Gallie BL, Squire JA, Goddard A et al. (1990) Biology of disease. Mechanism of oncogenesis in retinoblastoma.

Lab Invest 62: 394–408

Gao Y, Ferguson DO, Xie W et al. (2000) Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis,

genomic stability and development. Nature 404: 897–900

Garcia-Cao I, Garcia-Cao M, Martin-Caballero J et al. (2002) ‘Super p53’mice exhibit enhanced DNA damage

response, are tumor resistant and age normally. EMBO J 21: 6225–6235

Gardie B, Cayuela JM, Martini S et al. (1998) Genomic alterations of the p19ARF encoding exons in T-cell acute

lymphoblastic leukemia. Blood 91: 1016–1020

Garzon R, Fabbri M, Cimmino A et al. (2006) Micro RNA expression and function in cancer. Trends Mol. Med. 12:

580‒587

Garzon R, Volinia S, Liu CG et al. (2008) Micro RNA signatures associated with cytogenetics and prognosis in

acute myeloid leukemia. Blood 111: 3183‒3189

Gatei M, Young D, Cerosaletti KM et al. (2000) ATM-dependent phosphorylation of nibrin in response to radiation

exposure. Nature Genet 25: 115–118

Gavin AC, Bösche M, Krause R et al. (2002) Functional organization of the yeast proteome by systematic

analysis of protein complexes. Nature 415: 141–147

Gaya DR, Russell RK, Nimmo ER, Satsangi J (2007) New genes in inflammatory bowel disease: lessons for

complex diseases? Lancet 367: 1271‒1284

Gayther SA, Batley SJ, Linger L et al.(2000) Mutations truncating the EP300 acetylase in human cancers. Nature

Genet 24: 300–303

Gazin C, Wajapeyee N, Gobeil S , Virbasius CM, Green MR (2007) An elaborate pathway required for Ras-

mediated epigenetic silencing. Nature 449: 1073‒1077

German J (1993) Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine 72: 393–406

Giardiello FM, Yang VW, Hylind LM et al. 2002) Primary chemoprevention of familial adenomatous polyposis with

sulindac. N Engl J Med 346: 1054–1059

Gibbs JB (2000) Mechanism-based target identification and drug discovery in cancer research. Science 287:

1969–1973

Gimelbrant A, Hutchinson JN, Thompson BR, Chess A (2007) Widespread monallelic expression on human

autosomes. Science 318: 1136‒1140

Gleissner B, Gökbuget N, Bartram CR et al. (2002) Leading prognostic relevance of the BCR-ABL translocation in

adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and

confirmed polymerase chain reaction analysis. Blood 99: 1536–1543

Godar S, Ince TA, Bell GW et al. (2008) Growth-inhibitory and tumor-suppressive functions of p53 depend on its

repression of CD44 expression. Cell 134: 62‒73

Goh HS, Yao J, Smith DR (1995) p53 point mutation and survival in colorectal cancer patients. Cancer Res 55:

5217–5221

Goldberg Z, Sionov RV, Berger M et al. (2002) Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53

regulation. EMBO J 21: 3715–3727

Goldhirsch A, Glick JH, Gelber RD et al. (1998) Meeting highlights: international consensus panel on the

treatment of primary breast cancer. J Natl Cancer Inst 90:1601–1608

Goldstein AM, Fraser MC, Struewing JP et al. (1995) Increased risk of pancreatic cancer in melanoma-prone

kindreds with p16INK4a mutations. N Engl J Med 333: 970–974

Golub TR, Slonim DK, Tamayo P et al. (1999) Molecular classification of cancer: class discovery and class

prediction by gene expression monitoring. Science 286: 531–537

Gong JG, Costanzo A, Yang HQ et al. (1999) The tyrosine kinase c-Abl regulates p73 in apoptotic response to

cisplatin-induced DNA damage. Nature 399: 806–808

Goossens T, Klein U, Küppers R (1998) Frequent occurrence of deletions and duplications during somatic

hypermutation: implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci USA

95: 2463–2468

Gormally E, Vineis P, Matullo G et al. (2006) TP53 and KRAS2 mutations in plasma DNA of healthy subjects and

subsequent cancer occurence: a prospective study. Cancer Res. 66: 6871‒6876

Gorre ME, Mohammed M, Ellwood K et al. (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-

ABL gene mutation or amplification. Science 293: 876–880

Gottesman MM, Pastan I, Ambudkar SV (1996) P-glycoprotein and multidrug resistance. Curr Opin Genet Dev 6:

610–617

Gowen LC, Avrutskaya AV, Latour et al.(1998) BRCA1 required for transcription-coupled repair of oxidative DNA

damage. Science 281: 1009–1012

Page 9: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Graveley BR (2001) Alternative splicing: increasing diversity in the proteomic world. Trends Genet 17: 100–107

Grawunder U, Zimmer D, Fugmann S et al. (1998) DNA ligase IV is essential for V(D)J recombination and DNA

double-strand break repair in human precursor lymphocytes. Mol Cell 2: 477–484

Gray MD, Shen JC, Kamath-Loeb AS et al. (1997) The Werner syndrome protein is a DNA helicase. Nat Genet

17: 100–103

Gray NS, Wodicka L, Thunnissen AM et al. (1998) Exploiting chemical libraries, structure, and genomics in the

search for kinase inhibitors. Science 281: 533–538

Greenblatt MS, Bennett WP, Hollstein M et al. (1994) Mutations in the p53 tumor suppressor gene: clues to

cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878

Greenman C, Stephens P, Smith R et al. (2007) Patterns of somatic mutation in human cancer genomes. Nature

446: 153‒158

Greider CW (1999) Telomeres do D-Loop-T-Loop. Cell 97: 419–422

Griffith JD, Comeau L, Rosenfield S et al. (1999) Mammalian telomeres end in a large duplex loop. Cell 97: 503–

514

Grignani F, De Matteis S, Nervi C et al. (1998) Fusion proteins of the retinoic acid receptor- recruit histone

deacetylase in promyelocytic leukemia. Nature 391: 815–818

Groden J, Thliveris A, Samowitz W et al. (1991) Identification and characterization of the familial adenomatous

polyposis coli gene. Cell 66: 589–600

Groffen J, Stephenson JR, Heisterkamp N et al. (1984) Philadelphia chromosomal breakpoints are clustered

within a limited region, bcr, on chromosome 22. Cell 36: 93–99

Grompe M, D’Andrea AD (2001) Fanconi anemia and DNA repair. Hum Mol Genet 10: 2253–2259

Gu W, Roeder RG (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal

domain. Cell 90: 595–606

Gujral TS, Singh VK, Jia Z, Mulligan LM (2006) Molecular mechanisms of RET receptor mediated oncogenesis in

multiple endocrine neoplasia 2B. Cancer Res. 66: 10741‒10749

Gupta GP, Nguyen DX, Chiang AC et al. (2007) Mediators of vascular remodeling co-opted for sequential steps in

lung metastasis. Nature 446: 765‒770

Haber DA, Fearon ER (1998) The promise of cancer genetics. Lancet 351:1–8

Hafen E (1998) Kinases and phosphatases – a marriage is consummated. Science 280: 1212–1213

Hahn SA, Schutte M, Hoque AT et al. (1996) DPC4, a candidate tumor suppressor gene at human chromosome

18q21.1. Science 271: 350–353

Hahn WC, Weinberg RA (2002) Rules for making human tumor cells. N Engl Med 347: 1593–1603

Hahn WC, Counter CM, Lundberg AS et al. (1999) Creation of human tumour cells with defined genetic elements.

Nature 400: 464–468

Hainaut P, Pfeifer GP (2001) Patterns of p53 G→T transversions in lung cancers reflect the primary mutagenic

signature of DNA-damage by tobacco smoke. Carcinogenesis 22: 367–374

Halfon MS, Carmena A, Gisselbrecht S (2000) Ras pathway specificity is determined by the integration of multiple

signal-activated and tissue-restricted transcription factors. Cell 103: 63–74

Hallek M, Bergsagel PL, Anderson KC (1998) Multiple myeloma: increasing evidence for a multistep

transformation process. Blood 91: 3–21

Hampe J, Grebe J, Nikolaus S et al. (2002) Association of NOD2 (CARD 15) genotype with clinical course of

Crohn’s disease: a cohort study. Lancet 359: 1661–1665

Han HJ, Russo J, Kohwi Y et al. (2008) SATB1 reprogrammes gene expression to promote breast tumour growth

and metastasis. Nature 452: 187‒193

Hanada M, Delia D, Aiello A et al. (1993) bcl-2 gene hypomethylation and high-level expression in B-cell chronic

lymphocytic leukemia. Blood 82: 1820–1828

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57–70

Hanausek M, Ganesh P, Walaszek Z et al. (2001) Avicins, a family of triterpenoid saponins from Acacia victoriae

(Bentham), suppress H-ras mutations and aneuploidy in a murine skin carcinogenesis model. Proc Natl Acad

Sci USA 98: 11551–11556

Hann BC, Lane DP (1995) The dominating effect of mutant p53. Nature Genet 9: 221–222

Hansen RS, Wijmenga C, Luo P et al. (1999) The DNMT3B DNA methyltransferase gene is mutated in the ICF

immunodeficiency syndrome. Proc Natl Acad Sci USA 96: 14412–14417

Hark AT, Schoenherr CJ, Katz DJ et al. (2000) CTCF mediates methylationsensitive enhancer-blocking activity at

the H19/Igf2 locus. Nature 405: 486–489

Harley CB (2008) Telomerase and cancer therapeutics. Nature Rev. Cancer 8: 167‒179

Harris H, Miller OJ, Klein G et al. (1969) Suppression of malignancy by cell fusion. Nature 223: 363–368

Page 10: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Hashizume R, Fukuda M, Maeda I et al. (2001) The RING heterodimer BRCA1‒BARD1 is a ubiquitin ligase

inactivated by a breast cancer-derived mutation. J Biol Chem 276: 14537–14540

Haupt Y, Maya R, Kazaz A et al. (1997) Mdm2 promotes the rapid degradation of p53. Nature 387: 296–299

He L, He X, Lim LP et al. (2007) A micro RNA component of the p53 tumour suppressor network. Nature 447:

1130‒1134

He LZ, Tolentino T, Grayson P et al. (2001) Histone deacetylase inhibitors induce remission in transgenic models

of therapy-resistant acute promyelotic leukemia. J Clin Invest 108: 1321–30

He TC, Sparks AB, Rago C et al. (1998) Identification of c-MYC as a target of the APC pathway. Science 281:

1509–1512

Heard E, Rougeulle C, Arnaud D et al. (2001) Methylation of histone H3 at Lys-9 is an early mark on the X

chromosome during X inactivation. Cell 107: 727–738

Hedenfalk I, Duggan D, Chen Y et al. (2001) Gene-expression profiles in hereditary breast cancer. N Engl J Med

344: 539–548

Hegi ME, Diserens AC, Gorlia T et al. (2005) MGMT gene silencing and benefit from temozolomide in

glioblastoma. N. Engl. J. Med. 352: 997‒1003

Heighway J, Hasleton PS (1986) c-Ki-ras amplification in human lung cancer. Br J Cancer 53: 285–287

Hellman A, Zlotorynski E, Scherer SW et al. (2002) A role for common fragile site induction in amplification of

human oncogenes. Cancer Cell 1: 89–97

Heman MT, Bric A, Teruya-Feldstein J et al. (2005) Evasion of the p53 tumour surveillance network by tumour-

derived MYC mutants. Nature 436: 807‒811

Hemminki A, Markie D, Tomlinson I et al. (1998) A serine/threonine kinase gene defective in Peutz-Jeghers

syndrome. Nature 391: 184–187

Hendrick B, Bickmore W (2001) Human diseases with underlying defects in chromatin structure and modification.

Hum Mol Genet 20: 2233–2242

Hendrix MJC (2000) De-mystifying the mechanism(s) of maspin. Nature Med 6: 374–376

Herbig U, Jobling WA, Chen BPC et al. (2004) Telomer shortening triggers senescence of human cells through a

pathway involving ATM p53, and p21CIP1, but not p16INK4a. Mol. Cell 14: 501‒513

Herman JG, Latif F, Wenig Y et al. (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in

renal carcinoma. Proc Natl Acad Sci USA 91: 9700–9704

Herman JG, Merlo A, Mao L et al. (1995) Inactivation of the CDKN2/p16/ MTS1 gene is frequently associated with

aberrant DNA methylation in all common human cancers. Cancer Res 55: 4525–4530

Herman JG, Umar A, Polyak K et al. (1998) Incidence and functional consequences of hMLH1 promoter

hypermethylation in colorectal carcinoma. Proc Natl Acad Sci USA 95: 6870–6875

Herrmann C, Block C, Geisen C et al. (1998) Sulindac sulfide inhibits Ras signaling. Oncogene 17: 1769–1776

Hietanen S, Lain S, Krausz E et al. (2000) Activation of p53 in cervical carcinoma cells by small molecules. Proc

Natl Acad Sci USA 97: 8501–8506

Hilgers W, Kern SE (1999) Molecular genetic basis of pancreatic adenocarcinoma. Genes Chromosomes Cancer

26: 1–12

Hiom K, Melek M, Gellert M (1998) DNA transposition by the RAG1 and RAG2 proteins: a possible source of

oncogenic translocations. Cell 94: 463–470

Hirao A, Kong YY, Matsuoka S et al. (2000) DNA damage induced activation of p53 by the checkpoint kinase

Chk2. Science 287: 1824–1827

Hitchins MP, Wong JJl, Suthers G et al. (2007) Inheritance of a cancer-associated MLH1 germ-line epimutation.

N. Engl. J. Med. 356: 697‒705

Hochstraßer M (1996) Ubiquitin-dependent protein degradation. Annu Rev Genet 30: 405–439

Hodes R (2001) Molecular targeting of cancer: Telomeres as targets. Proc Natl Acad Sci USA 98: 7649–7651

Hoeijmakers JHJ (2001) Genome maintenance mechanisms for preventing cancer. Nature 411: 366–374

Hofmann WK, de Vos S, Elashoff D et al. (2002a) Relation between resistance of Philadelphia-chromosome-

positive acute lymphoblastic leukaemia to the tyrosine kinase inhibitor STI571 and gene-expression profiles: a

gene-expression study. Lancet 359: 481–486

Hofmann WK, Jones LC, Lemp NA et al. (2002b) Ph+ acute lymphoblastic leukemia resistant to the tyrosine

kinase inhibitor STI571 has a unique BCR-ABL gene mutation. Blood 99: 1860–1862

Honjo T, Muramatsu M, Fagarasan S (2004) AID: how does it aid antibody diversity? Immunity 20: 659‒668

Hooper ML (1998) Tumor suppressor gene mutations in humans and mice: parallels and contrasts. EMBO J 17:

6783–6789

Houlston RS, Tomlinson IPM (2000) Detecting low penetrance genes in cancer: the way ahead. J Med Genet 37:

161–167

Howe JR, Roth S, Ringold JC et al. (1998) Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science

280: 1086–1088

Page 11: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Howlett NG, Taniguchi T, Olson S et al. (2002) Billelic inactivation of BRCA2 in Fanconi anemia. Science 297:

606–609

Hsu IC, Metcalf RA, Sun T et al. (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas.

Nature 350: 427–428

Hu M, Yao J, Cai L et al. (2005) Distinct epigenetic changes in the stromal cells of breast cancers. Nature Genet.

37: 899‒905

Huang J, Papadopoulos N, McKinley AJ et al. (1996) APC mutations in colorectal tumors with mismatch repair

deficiency. Proc Natl Acad Sci USA 93: 9049–9054

Huang J, Perez-Burgos L, Placek BJ et al. (2006) Repression of p53 activity by Smyd2-Mediated methylation.

Nature 444: 629‒632

Huettner CS, Zhang P, van Etten RA et al. (2000) Reversibility of acute B-cell leukaemia induced by BCR-ABL1.

Nature Genet 24: 57–60

Hummel M, Bentink S, Berger H et al. (2006) A biologic definition of Burkitt’s lymphoma from transcriptional and

genomic profiling. N. Engl. J. Med. 354: 2419‒2430

Hunter T (1995) Protein kinases and phosphatases: the Ying and Yang of protein phosphorylation and signaling.

Cell 80: 225–236

Hunter T (1997) Oncoprotein networks. Cell 88: 333–346

Hunter T (2000) Signaling-2000 and beyond. Cell 100: 113‒127

Huse M, Kuriyan J (2002) The conformational plasticity of protein kinases. Cell 109: 275–282

Hussain SP, Harris CC (1998) Molecular epidemiology of human cancer: contribution of mutation spectra studies

of tumor suppressor genes. Cancer Res 58: 4023–4037

Husson SM, Hughes RAC (1994) The neurofibromatoses: a pathogenetic and clinical overview. Chapman & Hall,

London

Hussussian CJ, Struewing JP, Goldstein AM et al. (1994) Germline p16 mutations in familial melanoma. Nature

Genet 8: 15–21

Hüttenhofer A, Schattner P, Polacek (2008) Non-coding RNAs: hope or hype? Trends Genet. 21: 289‒297

Ichikawa A, Kinoshita R, Watanabe T et al. (1997) Mutations of the p53 gene as a prognostic factor in aggressive

B-cell lymphoma. N Engl J Med 337: 529–534

Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nature Rev Cancer 2: 277–

288

Imamura J, Miyoshi I, Koeffler HP (1994) p53 in hematologic malignancies. Blood 84: 2412–2421

International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human

genome. Nature 409: 860–921

International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human

genome. Nature 431: 931‒945

Ionov Y, Peinado MA, Malkhosyan S et al. (1993) Ubiquitous somatic mutations in single repeated sequences

reveal a new mechanism for colonic carcinogenesis. Nature 363: 558–561

Ionov Y, Yamamoto H, Krajewski S et al. (2000) Mutational inactivation of the proapoptotic gene BAX confers

selective advantage during tumor clonal evolution. Proc Natl Acad Sci USA 97: 10872–10877

Irby RB, Mao W, Coppola D et al. (1999) Activating SRC mutation in a subset of advanced human colon cancers.

Nature Genet 21: 187–190

Irwin M, Marin MC, Phillips AC et al. (2000) Role for the p53 homologue p73 in E2F-1‒induced apoptosis. Nature

407: 645–648

Ishikawa K, Takenaga K, Akimoto M et al. (2008) ROS-generating mitochondrial DNA mutations can regulate

tumor cell metastasis. Science 320: 661‒664

Jacobson S, Pillus L (1999) Modifying chromatin and concepts of cancer. Curr Opin Genet Dev 9: 175–184

Jänne PA, Mayer RJ (2000) Chemoprevention of colorectal cancer. N Engl J Med 342: 1960–1968

Jain M, Arvanitis C, Chu K et al. (2002) Sustained loss of a neoplastic phenotype by brief inactivation of MYC.

Science 297: 102–104

Jallepalli PV, Waizenegger IC, Bunz F et al.(2001) Securin is required for chromosomal stability in human cells.

Cell 105: 445–457

Jansen B, Schlagbauer-Wadl H, Kahr H et al. (1999) Novel Ras antagonist blocks human melanoma growth. Proc

Natl Acad Sci USA 96: 14019–14024

Jenuwein T, Allis CD (2001) Translating the histone code. Science 293: 1074–1080

Jin X, Nguyen D, Zhang WW et al. (1995) Cell cycle arrest and inhibition of tumor cell proliferation by the p16INK4a

gene mediated by an adenovirus vector. Cancer Res 55: 3250–3253

Jiricny J, Nyström-Lahti M (2000) Mismatch repair defects in cancer. Curr Opin Genet Dev 10: 157–161

Page 12: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nature Rev. Genet. 8:

253‒262

Joenje H, Patel KJ (2001) The emerging genetic and molecular basis of Fanconi anemia. Nature 2: 446–457

Johnson L, Mercer K, Greenbaum D et al. (2001) Somatic activation of the K-ras oncogene causes early onset

lung cancer in mice. Nature 410: 1111–1116

Johnson RE, Kondratick CM, Prakash S et al. (1999) hRAD30 mutations in the variant form of xeroderma

pigmentosum. Science 285: 263–265

Johnson SM, Grosshans H, Shingara J et al. (2005) RAS is regulated by the let-7 micro RNA family. Cell 120:

635‒647

Jones DH, Nakashima T, Sanchez DH et al. (2006) Regultion of cancer migration and bone metastasis by

RANKL. Nature 440: 692‒696

Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128: 683‒692

Jones S, Zhang X, Parsons DW et al. (2008) Core signaling pathways in human pancreatic cancers revealed by

global genomic analyses. Science 321: 1801‒1806

Jonkers J, Berns A (2002) Conditional mouse models of sporadic cancer. Nature Rev Cancer 2: 251–265

Judson H, Hayward BE, Sheridan E et al. (2002) A global disorder of imprinting in the human female germ line.

Nature 416: 539–542

Jüttermann R, Li E, Jaenisch R (1994) Toxicity of 5‒aza-2’-deoxycytidine to mammalian cells is mediated

primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci

USA 91: 11797–11801

Kadonaga JT (1998) Eukaryotic transcription: an interlaced network of transcription factors and chromatin-

modifying machines. Cell 92: 307–313

Kaghad M, Bonnet H, Yang A et al. (1997) Monoallelically expressed gene related to p53 at 1p36, a region

frequently deleted in neuroblastoma and other human cancers. Cell 90: 809–819

Kallioniemi A, Kallioniemi OP, Sudar D et al. (1992) Comparative genomic hybridization for molecular cytogenetic

analysis of solid tumors. Science 258: 818–821

Kalnina Z, Zayakin P, Line A (2005) Alterations of pre-m RNA splicing in cancer. Genes Chromosomes Cancer

42: 342‒357

Kanaar R, Hoeijmakers JHJ, van Gent DC (1998) Molecular mechanisms of DNA double-strand break repair.

Trends Cell Biol 8: 483–489

Kangaspeska S, Stride B, Metivier R et al. (2008) Transient cyclical methylation of promoter DNA. Nature 452:

112‒115

Karlseder J, Broccoli D, Dai Y et al. (1999) p53‒ and ATM-dependent apoptosis induced by telomeres lacking

TRF2. Science 283: 1321–1325

Karow JK, Constantinou A, Li JL et al. (2000a) The Bloom’s syndrome gene product promotes branch migration

of Holliday junctions. Proc Natl Acad Sci USA 97: 6504–6508

Karow JK, Wu L, Hickson ID (2000b) RecQ family helicases: roles in cancer and aging. Curr Opin Genet Dev 10:

32–38

Karuman P, Gozani O, Odze RD et al. (2001) The Peutz-Jegher gene product LKB1 is a mediator of p53-

Dependent cell death. Mol Cell 7: 1307–1319

Kastan MB, Lim DS (2000) The many substrates and functions of ATM. Nature Rev Mol Cell Biol 1: 179–186

Katsanis N, Ansley SJ, Badano JL (2001) Triallelic inheritance in Bardet-Biedl syndrome, a mendelian recessive

disorder. Science 293: 2256–2259

Katzenstein HM, Bowman LC, Brodeur GM et al. (1998) Prognostic significance of age, MYCNoncogene

amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric

oncology group experience – a pediatric oncology group study. J Clin Oncol 16: 2007–2017

Kawa K, Ohnuma N, Kaneko M et al. (1999) Long-term survivors of advanced neuroblastoma with MYCN amplification: a report of 19 patients surviving disease-free for more than 66 months. J Clin Oncol 10: 3216–

3220

Kawamata N, Ogawa S, Zimmermann M et al. (2008) Molecular allelokaryotyping of pediatric acute lymphoblastic

leukemias by high-resolution single nucleotide polymorphism oligonucleotide genomic microarray. Blood 111:

776‒784

Kerr P, Ashworth A (2001) New complexities for BRCA1 and BRCA2. Curr Biol 11: R668–R676

Khan J, Wei JS, Rignér M et al. (2001) Classification and diagnostic prediction of cancers using gene expression

profiling and artificial neural networks. Nature Med 7: 673–679

Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nature

Genet 27: 247–254

Khosravi R, Maya R, Gottlieb T et al.(1999) Rapid ATM-dependent phosphorylation of MDM 2 precedes p53

accumulation in response to DNA damage. Proc Natl Acad Sci USA 96: 14973–14977

Page 13: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Kim VN (2005) Micro RNA biogenesis: coordinated cropping and dicing. Nature Rev. Mol. Cell Biol. 6: 376‒385

Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87: 159–170

Kinzler KW, Vogelstein B (1997) Gatekeepers and caretakers. Nature 386: 761–763

Kirsch DG, Kastan MB (1998) Tumor-suppressor p53: implications for tumor development and prognosis. J Clin

Oncol 16: 3158–3168

Klugbauer S, Lengfelder E, Demidchik EP et al. (1995) High prevalence of RET rearrangement in thyroid tumors

of children from Belarus after the Chernobyl reactor accident. Oncogene 11: 2459–2467

Klugbauer S, Pfeiffer P, Gassenhuber H et al. (2001) RET rearrangements in radiation-induced papillary thyroid

carcinomas: high prevalence of topoisomerase I sites at breakpoints and microhomology-mediated end joining

in ELE1 and RET chimeric genes. Genomics 73: 149–160

Knudson AG (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68: 820–

823

Komarov PG, Komarova EA, Kondratov RV et al. (1999) A chemical inhibitor of p53 that protects mice from the

side effects of cancer therapy. Science 285: 1733–1737

Korsmeyer SJ (1992a) Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 80: 879–886

Korsmeyer SJ (1992b) Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes.

Annu Rev Immunol 10: 785–807

Krause DS, van Etten RA (2005) Tyrosine kinases as targets for cancer therapy. N. Engl. J. Med. 353:172‒187

Krek A, Grün D, Poy MN et al. (2005) Combinatorial micro RNA target predictions. Nature Genet. 37: 495‒500

Krimpenfort P, Quon KC, Mooi WJ (2001) Loss of p16INK4a confers susceptibility to metastatic melanoma in mice.

Nature 413:83–86

Krontiris TG, Cooper GM (1981) Transforming activity of human tumor DNAs. Proc Natl Acad Sci USA 78: 1181–

1184

Krützfeld J, Rajewsky N, Braich R et al. (2005) Silencing of micro RNAs in vivo with antagomirs. Nature 438:

685‒689

Kuipers J, Vaandrager JW, Weghuis DO et al. (1999) Fluorescence in situ hybridization analysis shows the

frequent occurrence of 14q32.3 rearrangements with involvement of immunoglobulin switch regions in

myeloma cell lines. Cancer Genet Cytogenet 109: 99–107

Kulozik AE, Hentze MW, Hagemeier C. Bartram CR (2000) Molekulare Medizin. Grundlagen –

Pathomechanismen – Klinik. De Gruyter, Berlin

Küppers R, Dalla-Favera R (2001) Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene

20: 5580–5594

Kwabi-Addo B, Giri D, Schmidt K et al. (2001) Haploinsufficiency of the Pten tumor suppressor gene promotes

prostate cancer progression. Proc Natl Acad Sci USA 98: 11563–11568

Landry JR, Mager DL, Wilhelm BT (2003) Complex controls: the role of the alternative promotors in mammilian

genomes. Trends Genet. 19: 640‒648

Lane DP (1984) Cell immortalization and transformation by the p53 gene. Nature 312: 596–597

Lane DP (1992) p53, guardian of the genome. Nature 358: 15–16

Langerak AW, Wolvers-Tettero ILM, van Gastel-Mol EJ et al. (2001) Basic helix-loop-helix proteins E2A and HEB

induce immature T-cell receptor rearrangements in nonlymphoid cells. Blood 98: 2456–2465

Lapointe J, Li C, Higgins JP et al. (2004) Gene expression profiling identifies clinically relevant subtypes of

prostate cancer. Proc. Natl. Acad. Sci. (USA) 101: 811‒816

Laurent E, Talpaz M, Kantarjian H et al. (2001) The BCR gene and Philadelphia chromosome-positive

leukemogenesis. Cancer Res 61: 2343–2355

Laurie NA, Donovan SL, Shih CS et al. (2006) Inactivation of the p53 pathway in retinoblastoma. Nature 444:

61‒66

Leach FS, Nicolaides NC, Papadopoulos N et al. (1993) Mutations of a mutS homolog in hereditary nonpolyposis

colorectal cancer. Cell 75: 1215–1225

Leary RJ, Lin JC, Cummings J et al. (2008) Integrated analysis of homozygous deletions, focal amplifications and

sequence alterations in breast an colorectal cancers. Proc Natl Acad Sci USA 105: 16224-9

Lee JH, Pauli TT (2005) ATM activation by DNA double-strand breaks through the Mre11‒Rad50‒Nbs1 complex.

Science 308: 551‒554

Lee S-K, Yu S-L, Prakash L et al. (2002) Requirement of yeast RAD2, a homolog of human XPG gene, for

efficient RNA polymerase II transcription: implications for Cockayne syndrome. Cell 109: 823–834

Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396: 643–649

Leon J, Kamino H, Steinberg JJ et al. (1988) H-ras activation in benign and self-regressing skin tumors

(keratoacanthomas) in both humans and an animal model system. Mol Cell Biol 8: 786–793

Leung SY, Yuen ST, Chung LP et al. (1999) hMLH1 promoter methylation and lack of hMLH1 expression in

sporadic gastric carcinomas with highfrequency microsatellite instability. Cancer Res. 59: 159–164

Page 14: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Levens D (2002) Disentangling the MYC web. Proc Natl Acad Sci USA 99: 5757–5759

Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88: 323–331

Lewis SM (1994) The mechanism of V(D)J joining: lessons from molecular, immunological, and comparative

analyses. Adv Immunol 56: 27–150

Lewis SM, Agard E, Suh S et al. (1997) Cryptic signals and the fidelity of V(D)J joining. Mol Cell Biol 17: 3125–

3136

Leyland-Jones B (2002) Trastuzumab: hopes and realities. Lancet Oncol 3: 137–144

Li H, Wang J, Mor G, Sklar J (2008) A neoplastic gene fusion mimics trans-splicing of RNAs in normal human

cells. Science 321: 1357‒1361

Li M, Chen D, Shiloh A et al. (2002) Deubiquitination of p53 by HAUSP is an important pathway for p53

stabilization. Nature 416: 648–653

Li S, Ting NSY, Zheng L et al. (2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA

damage response. Nature 406: 210–215

Li YM, Pan Y, Wei Y et al (2004) Upregulation of CXCR4 in essential for HER2-Mediated tumor metastasis.

Cancer Cell 6: 459‒469

Lichtenstein P, Holm NV, Verkasalo PK et al. (2000) Environmental and heritable factors in the causation of

cancer. N Engl J Med 343: 78–85

Liggett WH, Sidransky D (1998) Role of the p16 tumor suppressor gene in cancer. J Clin Oncol 16: 1197–1206

Lin SY, Makino K, Xia W et al. (2001) Nuclear localization of EGF receptor and its potential new role as a

transcription factor. Nature Cell Biol 3: 802–808

Lin Y, Ma W, Benchimol S (2000) Pidd, a new death-domain-containing protein, is induced by p53 and promotes

apoptosis. Nature Genet 26: 122–125

Lindblom A (2001) Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin

Oncol 13: 63–69

Linggi B, Müller-Tidow C, van de Locht L et al. (2002) The t (8;21) fusion protein, AML1‒ETO, specifically

represses the transcription of the p14ARF tumor suppressor in acute myeloid leukemia. Nat Med 8: 743–750

Lingle, WL, Barrett SL, Negron VC et al. (2002) Centrosome amplification drives chromosomal instability in breast

tumor development. Proc Natl Acad Sci USA 99: 1978–1983

Lipkin SM, Rozek LS, Rennert G et al. (2004) The MLH1 D132H variant is associated with susceptibility to

sporadic colorectal cancer. Nature Genet. 36: 694‒699

Lipton L, Halford SE, Johnson V et al. (2003) Carcinogenesis in MYH-associated polyposis follows a distinct

genetic pathway. Cancer Res. 63: 7595‒7599

Lissy NA, Davis PK, Irwin M et al. (2000) A common E2F-1 and p73 pathway mediates cell death induced by TCR

activation. Nature 407: 642–644

Liu M, Duke JL, Richter DJ et al. (2008) Two levels of protection for the B cell genome during somatic

hypermutation. Nature 451: 841‒845

Loeb LA (1991) Mutator phenotype may be required for multistage carcinogenesis. Cancer Res 51: 3075–3075

Loeb LA (2001) A mutator phenotype in cancer. Cancer Res 61:3230–3239

Lohmann DR, Brandt B, Höpping W et al. (1996) The spectrum of RB1 germline mutations in hereditary

retinoblastoma. Am J Hum Genet 58: 940–949

Lothe RA (1997) Microsatellite instability in human solid tumors. Mol Med Today 3: 61–68

Louis DN, Holland EC, Cairncross JG (2001) Glioma classification: a molecular reappraisal. Am J Pathol 159:

779–786

Lovett BD, Lo Nigro L, Rappaport EF et al. (2001) Near-precise interchromosomal recombination and functional

DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute

lymphoblastic leukemia with t (4;11) translocation. Proc Natl Acad Sci USA 98: 9804–9807

Lowenstein EJ, Daly RJ, Batzer AG et al. (1992) The SH2 and SH3 domaincontaining protein GRB2 links

receptor tyrosine kinases to ras signaling. Cell 70: 431–442

Lowy DR, Willumsen BM (1993) Function and regulation of ras. Annu Rev Biochem 62: 851–891

Lu J, Getz G, Miska EA et al (2005) Micro RNA expression profiles classify human cancers. Nature 435: 834‒838

Lujambio A, Ropero S, Ballestar et al. (2007) Genetic unmasking of an epigenetically silenced micro RNA in

human cancer cells. Cancer Res. 67: 1424‒1429

Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential

modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18: 753–761

Luo G, Santoro IM, McDaniel LD et al. (2000) Cancer predisposition caused by elevated mitotic recombination in

Bloom mice. Nature Genet 26: 424–429

Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in

breast cancer. Nature 449: 682‒688

Page 15: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Ma Y, Pannicke U, Schwarz K et al. (2002) Hairpin and overhang processing by an Artemins/DNA-dependent

protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 108: 781–794

Macleod K (2000) Tumor suppressor genes. Curr Opin Genet Dev 10:81–93

MacPhee M, Chepenik KP, Liddell RA et al. (1995) The secretory phospholipase A2 gene is a candidate for the

Mom1 locus, a major modifier of APCMin-induced intestinal neoplasia. Cell 81: 957–966

Madhani HD (2001) Accounting for specificity in receptor tyrosine kinase signaling. Cell 106: 9–11

Magee T, Marshall C (1999) New insights into the interaction of Ras with the plasma membrane. Cell 98: 9–12

Maher ER, Reik W (2000) Beckwith-Wiedemann syndrome: imprinting in clusters revisited. J Clin Invest 105:

247–252

Maina F, Panté G, Helmbacher F et al. (2001) Coupling met to specific pathways results in distinct developmental

outcomes. Mol Cell 7: 1293–1306

Maizels N (1999) Immunoglobulin class switch recombination: will genetics provide new clues to mechanism? Am

J Hum Genet 64: 1270–1275

Malkin D (1994) Germline p53 mutations and heritable cancer. Annu Rev Genet 28: 443–465

Malliri A, van der Kammen RA, Clark K et al (2002) Mice deficient in the Rac activator Tiam1 are resistant to Ras-

induced skin tumours. Nature 417: 867–871

Manié S, Santoro M, Fusco A et al. (2001) The RET receptor: function in development and dysfunction in

congenital malformation. Trends Genet 17: 580–589

Marculescu R, Le T, Simon P et al. (2002) V(D)J-mediated translocations in lymphoid neoplasms: a functional

assessment of genomic instability by cryptic sites. J Exp Med 195: 85–98

Margueron R, Trojer P, Reinberg D (2005) The key to development: interpreting the histone code? Curr. Opin.

Genet. Develop. 15: 163‒176

Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in microfabricated high-density picolitre

reactors. Nature 437: 376‒380

Marin MC, Jost CA, Brooks LA et al. (2000) A common polymorphism acts as an intragenic modifier of mutant

p53 behaviour. Nature Genet 25: 47–54

Maris JM, Matthay KK (1999) Molecular biology of neuroblastoma. J Clin Oncol 7: 2264–2279

Markowitz S, Wang J, Myeroff L et al. (1995) Inactivation of the Type II TGF- receptor in colon cancer cells with

microsatellite instability. Science 268: 1336–1338

Marmorstein LY, Ouchi T, Aaronson SA (1998) The BRCA2 gene product functionally interacts with p53 and

RAD51. Proc Natl Acad Sci USA 95: 13869–13874

Marnett LJ, Plastaras JP (2001) Endogenous DNA damage and mutation. Trends Genet 17: 214–221

Marrone A, Walne A, Dokal I (2005) Dyskeratosis congenita: telomerase, telomeres and anticipation. Curr. Opin.

Genet. Develop. 15: 249‒257

Martin GM, Oshima J (2000) Lessons from human progeroid syndromes. Nature 408: 263–266

Martinez LA, Naguibneva I, Lehrmann H et al. (2002) Synthetic small inhibiting RNAs: Efficient tools to inactivate

oncogenic mutations and restore p53 pathways. Proc Natl Acad Sci USA 99: 14849–14854

Martins CP, Brown-Swigart L, Evan GI (2006) Modeling the therapeutic efficacy of p53 restoration in tumors. Cell

127: 1323‒1334

Matolcsy A, Casali P, Warnke RA et al. (1996) Morphologic transformation of follicular lymphoma is associated

with somatic mutation of the translocated Bcl-2 gene. Blood 88: 3937–3944

Matsuzaki K, Deng G, Tanaka H et al (2005) The relationship between global methylation level, loss of

heterozygosity, and microsatellite instability in sporadic colorectal cancer. Clin. Cancer Res. 11: 8564‒8569

Mayo LD, Donner DB (2001) A phosphatidylinositol 3‒kinase/Akt pathway promotes translocation of Mdm2 from

the cytoplasm to the nucleus. Proc Natl Acad Sci USA 98: 11598–11603

McCarroll SA, Altshuler DM (2007) Copy-number variation and association studies of human diseases. Nature

Genet. 39: 537‒542

McGrath J, Solter D (1984) Completion of mouse embryogenesis requires both the maternal and paternal

genomes. Cell 37: 179–183

McManus MT, Sharp PA (2002) Gene silencing in mammals by small interfering RNAs. Nature Rev Genet 3: 737–

747

McMurry MT, Krangel MS (2000) A role for histone acetylation in the developmental regulation of VDJ

recombination. Science 287: 495–498

Megonigal MD, Cheung NK, Rappaport EF et al. (2000) Detection of leukemia-associated MLL-GAS7

translocation early during chemotherapy with DNA topoisomerase II inhibitors. Proc Natl Acad Sci USA 97:

2814–2819

Meister G, Tuschl T (2004) Mechanisms of gene silencing by double-stranded RNA. Nature 431: 343‒349

Melnick A, Licht JD (1999) Deconstructing a disease: RAR , its fusion partners, and their roles in the athogenesis

of acute promyelocytic leukemia. Blood 93: 3167–3215

Page 16: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Menssen A, Hermeking H (2002) Characterization of the c-MYC-regulated transcriptome by SAGE: identification

and analysis of c-MYC target genes. Proc Natl Acad Sci USA 99: 6274–6279

Meyerson M (2000) Role of telomerase in normal and cancer cells. J Clin Oncol. 18: 2626–2634

Meyn MS (1999) Ataxia-telangiectasia, cancer and the pathobiology of the ATM gene. Clin Genet 55: 289–304

Mi S, Lu J, Sun M et al. (2007) Micro RNA expression signatures accurately discriminate acute lymphoblastic

leukemia from acute myeloid leukemia. Proc. natl. Acad. Sci. (USA) 104: 19971‒19976

Michel LS, Liberal V, Chatterjee A et al. (2001) MAD2 haplo-insufficiency causes premature anaphase and

chromosome instability in mammalian cells. Nature 409: 355–359

Michaloglou C, Vredeveld LCM, Soengas MS et al. (2005) BRAFE600‒associated senescence-like cell cycle arrest

of human naevi. Nature 436: 720‒724

Michiels F, Habets GG, Stam J et al. (1995) A role for Rac in Tiam1‒induced membrane ruffling and invasion.

Nature 375: 338–340

Michikawa Y, Mazzucchelli F, Bresolin N et al. (1999) Aging-dependent large accumulation of point mutations in

the human mtDNA control region for replication. Science 286: 774–779

Michishita E, McCord RA, Berber E et al. (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates

telomeric chromatin. Nature 452: 492‒496

Mitchell PS, Parkin RK, Kroh EM et al. (2008) Circulating microRNAs as stable blood-based markers for cancer

detection. Proc. Natl. Acad. Sci. (USA) 105: 10513‒10518

Mitelman F, Johansson B, Mertens F (2007) The impact of translocations and gene fusions on cancer causation.

Nature Rev. Cancer 7: 233‒245

Mitelman F, Mertens F, Johansson B (1997) A breakpoint map of recurrent chromosomal rearrangements in

human neoplasia. Nat Genet 15: 417–74

Miyakura Y, Sugano K Konishi F et al. (2001) Extensive methylation of hMLH1 promoter region predominates in

proximal colon cancer with microsatellite instability. Gastroenterology 121: 1300–1309

Miyoshi Y, Nagase H, Ando H et al. (1992) Somatic mutations of the APC gene in colorectal tumors: mutation

cluster region in the APC gene. Hum Mol Genet 1: 229–233

Moodie SA, Willumsen BM, Weber MJ et al. (1993) Complexes of Ras•GTP with Raf-1 and mitogen-activated

protein kinase kinase. Science 260: 1658–1661

Morales CP, Holt SE, Ouellette M et al. (1999) Absence of cancer-associated changes in human fibroblasts

immortalized with telomerase. Nature Genet 21: 115–117

Morgan GH, Hughes T, Janssen JWG et al. (1989) Polymerase chain reaction for detection of residual leukaemia.

Lancet 1: 928–929

Mori Y, Sato F, Selaru FM et al. (2002) Instabilotyping reveals unique mutational spectra in microsatellite-unstable

gastric cancers. Cancer Res 62: 3641–3645

Morin PJ, Sparks AB, Korinek V et al. (1997) Activation of -catenin-Tcf signaling in colon cancer by mutations in

-catenin or APC. Science 275: 1787–1790

Mortuza FY, Papaioannou M, Moreira IM et al. (2002) Minimal residual disease tests provide an independent

predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol 20: 1094–1104

Moshous D, Callebaut I, de Chasseval R et al. (2001) Artemis, a novel DNA double-strand break repair/V(D)J

recombination protein, is mutated in human severe combined immune deficiency. Cell 105: 177–1786

Mrozek K, Marcucci G, Paschka P et al. (2007) Clinical relevance of mutations and gene expression changes in

adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular

classification? Blood 109: 431‒448

Mullighan CG, Goorha S, Radtke I et al. (2007) Genome-wide analysis of genetic alternations in acute

lymphoblastic leukemia. Nature 446: 758‒764

Münger K, Werness BA, Dyson N et al. (1989) Complex formation of human papillomavirus E7 proteins with the

retinoblastoma tumor suppressor gene product. EMBO J 8: 4099–4105

Muramatsu M, Kinoshita K, Fagarasan S et al. (2000) Class switch recombination and hypermutation require

activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553–563

Murphy MJ, Wilson A, Trumpp A (2005) More than just proliferation: MYC function in stem cells. Trends Cell Biol.

15: 128‒137

Murray MJ, Shilo BZ, Shih C et al. (1981) Three different human tumor cell lines contain different oncogenes. Cell

25: 355–361

Nagata Y, Lan KH, Zhou X et al. (2004) PTEN activation contributes to tumor inhibition by trastuzumab, and loss

of PTEN predicts trastuzumab resistance in patients. Cancer Cell 6: 117‒127

Nakagawa H, Chadwick RB, Peltomäki P et al. (2001) Loss of imprinting of the insulin-like growth factor II gene

occurs by biallelic methylation in a core region of H19‒associated CTCF-binding sites in colorectal cancer.

Proc Natl Acad Sci USA 98: 591–596

Page 17: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Nakazawa H, English D, Randell PL et al. (1994) UV and skin cancer: specific p53 gene mutation in normal skin

as a biologically relevant exposure measurement. Proc Natl Acad Sci USA 91: 360–364

Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nature Rev. Cancer 4: 665‒676

Nebert DW (1999) Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin

Genet 56: 247–258

Nekhaeva E, Bodyak ND, Kraytsberg Y et al. (2002) Clonally expanded mtDNA point mutations are abundant in

individual cells of human tissues. Proc Natl Acad Sci USA 99: 5521–5526

Nelson MA, Futscher BW, Kinsella T et al. (1992) Detection of mutant Ha-ras genes in chemically initiated mouse

skin epidermis before the development of benign tumors. Proc Natl Acad Sci USA 89: 6398–6402

Nguyen DX, Massague J (2007) Genetic determinants of cancer metastasis. Nature Rev. Genet. 8: 341‒352

Nielsen TO, West RB, Linn SC et al. (2002) Molecular characterisation of soft tissue tumours: a gene expression

study. Lancet 359: 1301–1307

Nielsen, SJ, Schneider R, Bauer UM et al. (2001) Rb targets histone H3 methylation and HP1 to promoters.

Nature 412: 561–565

Nikolaev AY, Li M, Puskas N et al. (2003) Parc: a cytoplasmic anchor for p53. Cell 112: 29–40

Nishida, T, Hirota S, Taniguchi M et al. (1998) Familial gastrointestinal stromal tumours with germline mutation of

the KIT gene. Nature Genet 19:323–324

Nissim-Rafinia M, Kerem B (2002) Splicing regulation as a potential genetic modifier. Trends Genet 18: 123–127

Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194: 23–28

Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:

1497

Oberthuer A, Berthold F, Warnat P et al. (2006) Customized olignucleotide microarray gene excpression-based

classification of neuroblastom patients outperforms current clinical risk stratification. J. Clin. Oncol. 31:

5070‒5078

Oda E, Ohki R, Murasawa H et al. (2000a) Noxa, a BH3‒only member of the Bcl-2 family and candidate mediator

of p53‒induced apoptosis. Science 288: 1053–1058

Oda K, Arakawa H, Tanaka T et al. (2000b) p53AIP1, a potential mediator of p53-Dependent apoptosis, and its

regulation by Ser-46‒phosphorylated p53. Cell 102, 849–862

O’Donnell K, Wentzel EA, Zeller KI et al. (2005) c-MYC-regulated microRNAs modulate E2F1 expression. Nature

435: 839‒843

O’Driscoll M, Cerosaletti KM, Girard PM et al. (2001) DNA ligase IV mutations identified in patients exhibiting

developmental delay and immunodeficiency. Mol Cell 8: 1175–1185

O’Driscoll M, Jeggo PA (2006) The role of double-strand break repair – insights from human genetics. Nature

Rev. Genet. 7: 45‒54

Oettinger MA, Schatz DG, Gorka C et al. (199) RAG-1 and RAG-2, adjacent genes that synergistically activate

V(D)J recombination. Science 248: 1517–1523

Oliner JD, Kinzler KW, Meltzer PS et al.(1992) Amplification of a gene encoding a p53‒associated protein in

human sarcomas. Nature 358: 80–83

Orimo A, Gupta PB, Sgroi DC et al. (2005) Stromal fibroblasts present in invasive human breast carcinomas

promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121: 335‒348

Pao GM, Janknecht R, Ruffner H et al. (2000) CBP/p300 interact with and function as transcriptional coactivators

of BRCA1. Proc Natl Acad Sci USA 97: 1020–1025

Papadopoulos N, Nicolaides NC, Wei YF et al. (1994) Mutation of a mutl homolog in hereditary colon cancer.

Science 263: 1625–1629

Papavasiliou FN, Schatz DG (2000) Cell-cycle-regulated DNA doublestrand breaks in somatic hypermutation of

immunoglobulin genes. Nature 408: 216–221

Papavasiliou FN, Schatz DG (2002) Somatic hypermutation of immunoglobulin genes: merging mechanisms for

genetic diversity. Cell 109: S35‒S44

Parada LF, Tabin CJ, Shih C et al. (1982) Human EJ bladder carcinoma oncogene is a homologue of Harvey

sarcoma virus ras gene. Nature 297: 474–477

Parson R, Li GM, Longley et al. (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell

75: 1227–1236

Parsons DW, Jones S, Zhang X et al. (2008) An integrated genomic analysis of human glioblastoma multiforme.

Science 321: 1807‒1812

Pasini B, Ceccherini I, Romeo G (1996) RET mutations in human disease. Trends Genet 12: 138–144

Pasqualucci L, Migliazza A, Fracchiolla N et al. (1998) BCL-6 mutations in normal germinal center B cells:

evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci USA 95: 11816–11821

Pasqualucci L, Neumeister P, Goossens T et al. (2001) Hypermutation of multiple proto-oncogenes in B-cell

diffuse large-cell lymphomas. Nature 412: 341–346

Page 18: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Patocs A, Zhang L, Yaomin X et al. (2007) Breast-cancer stromal cells with TP53 mutations and nodal

metastases. N. Engl. J. Med. 357: 2543‒2551

Pawson T (1995) Protein modules and signalling networks. Nature 373: 573–580

Pawson T, Scott JD (1997) Signaling through scaffold, anchoring, and adaptor proteins. Science 278: 2075–2080

Peinado MA, Malkhosyan S, Velazquez A et al. (1992) Isolation and characterization of allelic losses and gains in

colorectal tumors by arbitrarily primed polymerase chain reaction. Proc Natl Acad Sci USA 89: 10065–10069

Pelengaris S, Littlewood T, Khan M et al. (1999) Reversible activation of c-Myc in skin: induction of a complex

neoplastic phenotype by a single oncogenic lesion. Mol Cell 3: 565–577

Pellegrini L, Yu DS, Lo T et al. (2002) Insights into DNA recombination from the structure of a RAD51‒BRCA2

complex. Nature 420: 287–293

Perou CM, Sorlie T, Eisen MB et al. (2000) Molecular portraits of human breast tumours. Nature 406: 747–752

Peters JM (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9: 931–943

Petrij F, Giles RH, Dauwerse HG et al. (1995) Rubinstein-Taybi syndrome caused by mutations in the

transcriptional co-activator CBP. Nature 376:348–351

Petros JA, Baumann AK, Ruiz-Pesini E et al. (2005) mt DNA mutations increase tumorgenicity in prostate cancer.

Proc. Natl. Acad. Sci. (USA) 102: 719‒724

Pinkel D, Segraves R, Sudar D et al. (1998) High resolution analysis of DNA copy number variation using

comparative genomic hybridization to microarrays. Nature Genet 20: 207–211

Plass C, Soloway PD (2002) DNA methylation, imprinting and cancer. Eur J Hum Genet 10: 6–16

Plaza-Menacho I, Burzynski GM, de Groot JW, Eggen BJL, Hofstra BMW (2006) Current concepts in RET-related

genetics, signaling and therapeutics. Trends. Genet. 22: 627‒636

Pluk H, Dorey K, Superti-Furga G et al. (2002) Autoinhibition of c-Abl. Cell 108: 247–259

Polyak K, Li Y, Zhu H et al. (1998) Somatic mutations of the mitochondrial genome in human colorectal tumours.

Nature Genet 20:291–293

Polyak K, Xia Y, Zweier JL et al. (1997) A model for p53‒induced apoptosis. Nature 389: 300–305

Pomeroy SL, Tamayo P, Gaasenbeek M et al. (2002) Prediction of central nervous system embryonal tumour

outcome based on gene expression. Nature 415: 436–442

Ponder B (1988) Gene losses in human tumors. Nature 335: 400–402

Ponder BA (1999) The phenotypes associated with ret mutations in the multiple endocrine neoplasia type 2

syndrome. Cancer Res 59: 1736s–1742s

Pongers-Willemse MJ, Seriu T, Stolz F et al. (1999) Primers and protocols for standardized detection of minimal

residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene

rearrangements and TAL1 deletions as PCR targets. Report of the BIOMED-1 CONCERTED ACTION:

investigation of minimal residual disease in acute leukemia. Leukemia 13: 110–118

Potti A, Dressman HK, Bild A et al. (2006) Genomic signatures to guide the use of chemotherapeutics. Nature

Med. 11: 1294‒1300

Prescott SM, White RL (1996) Self-promotion? Intimate connections between APC and prostaglandin H synthase-

2. Cell 87: 783–786

Prives C (1998) Signaling to p53: breaking the MDM 2‒p53 circuit. Cell 95: 5–8

Qiu W, Hu M, Scridhar A et al. (2008) No evidence of clonal somatic genetic alterations in cancer-associated

fibroblasts from human breast and ovarian carcinomas. Nature Genet. 40: 650‒655

Quackenbush J (2006) Microarray analysis and tumor classification. N. Engl. J. Med. 354: 2463‒2472

Quelle DE, Zindy F, Ashmun RA et al. (1995) Alternative reading frames of the INK4a tumor suppressor gene

encode two unrelated proteins capable of inducing cell cycle arrest. Cell 83: 993–1000

Quintanilla M, Brown K, Ramsden M et al. (1986) Carcinogen-specific mutation and amplification of Ha-ras during

mouse skin carcinogenesis. Nature 322: 78–80

Raj K, Ogston P, Beard P (2001) Virus-mediated killing of cells that lack p53 activity. Nature 412: 914–917

Rajagopalan H, Lengauer C (2004) Aneuploidy and cancer. Nature 432: 338‒341

Ramaswamy S, Ross KN, Lander ES et al. (2003) A molecular signature of metastasis in primary solid tumors.

Nature Genet 33: 49–54

Rampino N, Yamamoto H, Ionov Y et al. (1997) Somatic frameshift mutations in the BAX gene in colon cancers of

the microsatellite mutator phenotype. Science 275: 967–969

Rebollo A, Martinez-A C (1999) Ras proteins: recent advances and new functions. Blood 94: 2971–2980

Redner RL, Wang J, Liu JM (1999) Chromatin remodeling and leukemia: new therapeutic paradigms. Blood 94:

417–428

Redon R, Ishikawa S, Fitch KR et al. (2006) Global variation in copy number in the human genome. Nature 444:

444‒454

Reich DE, Lander ES (2001) On the allelic spectrum of human disease. Trends Genet 17: 502–510

Page 19: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Reik W, Kelsey G, Walter J (1999) Dissecting de novo methylation. Nature Genet 23: 380–382

Reik W, Walter J (2001) Genomic imprinting: parental influence on the genome. Nature Genet 2: 21–32

Reis RM, Könü-Lebleblicioglu D, Lopes JM et al. (2000) Genetic profile of gliosarcomas. Am J Pathol 156 425–

432

Reiss T (2001) Drug discovery of the future: the implications of the human genome project. Trends Biotechnol 19:

496–499

Renan MJ (1993) How many mutations are required for tumorigenesis? Implications from human cancer data. Mol

Carcinog 7: 139–146

Renwick A, Thompson D, Seal S et al. (2006) ATM mutations that cause ataxia-teleangiectasin are breast cancer

susceptibility alleles. Nature Genet. 38: 873‒875

Revy P, Muto T, Levy Y et al. (2000) Activation-induced cytidine deaminase (AID) deficiency causes the

autosomal recessive form of the hyper-IgM syndrome (HIGM2). Cell 102: 565–575

Ribeiro RC, Sandrini F, Figueiredo B et al. (2001) An inherited p53 mutation that contributes in a tissue-specific

manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA 98: 9330–9335

Rich T, Allen RL, Wyllie AH (2000) Defying death after DNA damage. Nature 407: 777–783

Richardson C, Jasin M (2000) Frequent chromosomal translocations induced by DNA double-strand breaks.

Nature 405: 697–700

Richon VM, O’Brien JP (2002) Histone deacetylase inhibitors: a new class of potential therapeutic agents for

cancer treatment. Clin Cancer Res 8: 662–664

RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core

Group) and the FANTOM Consortium (2005) Antisense transcription in the mammalian transcriptome. Science

309: 1564‒1566

Rizki A, Lundblad V (2001) Defects in mismatch repair promote telomerase-independent proliferation. Nature 411:

713–716

Robbiani DF, Bothmer A, Callen E et al. (2008) AID is requie for the chromosomal breaks in c-myc that lead to c-

myc/IgH translations. Cell 135: 1028-38

Robert M-F, Morin S, Beaulieu N et al.(2003) DNMT1 is required to maintain CpG methylation and aberrant gene

silencing in human cancer cells. Nature Genet 33: 61–65

Robertson KD (2002) DNA methylation and chromatin – unraveling the tangled web. Oncogene 21: 5361–5379

Robertson KD, Ait-Si-Ali S, Yokochi T et al. (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and

represses transcription from E2F-responsive promoters. Nature Genet 25: 338–342

Roman-Gomez J, Jimenez-Velasco A, Costillejo JA et al. (2004) Promotor hypermethylation of cancer-related

genes: a strong independent prognostic factor in acute lymphoblastic leukemia. Blood 104: 2492‒2498

Romanow WJ, Langerak AW, Goebel P et al. (2000) E2A and EBF act in synergy with the V(D)J recombinase to

generate a diverse immunoglobulin repertoire in nonlymphoid cells. Mol Cell 5: 343–353

Rommel C, Clarke BA, Zimmermann S et al. (1999) Differentiation stage-specific inhibition of the Raf-MEK-ERK

pathway by Akt. Science 286: 1738–1741

Ropero S, Fraga MF, Ballestar E et al. (2006) A truncating mutation of HDAC2 in human cancers confers

resistance to histone deacetylase inhibition. Nature Genet. 38: 566‒569

Rosell R, Li S, Skacel Z et al.(1993) Prognostic impact of mutated K-ras gene in surgically resected non-small cell

lung cancer patients. Oncogene 8: 2407–2412

Rosenwald A, Wright G, Chan WC et al. (2002) The use of molecular profiling to predict survival after

chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346: 1937–1947

Roth JA, Nguyen D, Lawrence DD et al. (1996) Retrovirus-mediated wildtype p53 gene transfer to tumors of

patients with lung cancer. Nature Med 2: 985–991

Rowinsky EK, Windle JJ, von Hoff DD (1999) Ras protein farnesyltransferase: A strategic target for anticancer

therapeutic development. J Clin Oncol 17: 3631–3652

Rowley JD (1973) Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia

identified by quinacrine fluorescence and Giemsa staining. Nature 243: 290–293

Rowley JD, Reshmi S, Sobulo O et al. (1997) All patients with the T(11;16)(q23;p13.3) that involves MLL and

CBP have treatment-related hematologic disorders. Blood 90: 535–541

Roy F, Therrien M (2002) MAP kinase module: the Ksr connection. Curr Biol 12: R325–R327

Roz L, Wu CL, Porter S et al. (1996) Allelic imbalances on chromosome 3p in oral dysplastic lesions: an early

event in oral carcinogenesis. Cancer Res 56: 1228–1231

Rudolph KL, Chang S, Lee HW et al. (1999) Longevity, stress response, and cancer in aging telomerase-deficient

mice. Cell 96: 701–712

Ruffner H, Joazeiro CAP, Hemmati D et al. (2001) Cancer-predisposing mutations within the RING domain of

BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity. Proc Natl Acad

Sci USA 98: 5134–5139

Page 20: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Rüschoff J, Wallinger S, Dietmaier W et al. (1998) Aspirin suppresses the mutator phenotype associated with

hereditary nonpolyposis colorectal cancer by genetic selection. Proc Natl Acad Sci USA 95: 11301–11306

Ruttledge MH, Sarrazin J, Rangaratnam S et al. (1994) Evidence for the complete inactivation of the NF2 gene in

the majority of sporadic meningiomas. Nature Genet 6: 180–184

Saha S, Bardelli A, Buckhaults P et al. (2001) A phosphatase associated with metastasis of colorectal cancer.

Science 294: 13431346

Samuels-Lev Y, O’Connor DJ, Bergamaschi D et al. (2001) ASPP proteins specifically stimulate the apoptotic

function of p53. Mol Cell 8: 781–794

Sandig V, Brand K, Herwig S et al. (1997) Adenovirally transferred p16INK4/CDKN2 and p53 genes cooperate to

induce apoptotic tumor cell death. Nature Med 3: 313–319

Sassone-Corsi P, Mizzen CA, Cheung P et al. (1999) Requirement of Rsk-2 for epidermal growth factor-activated

phosphorylation of histone H3. Science 285: 886–891

Savage DG, Antman KH (2002) Imatinib mesylate – a new oral targeted therapy. N Engl J Med 346: 683–693

Savitsky K, Bar-Shira A, Gilad S et al. (1995) A single ataxia telangiectasia gene with a product similar to PI-3

kinase. Science 268: 1749–1753

Sawyers CL (2002) Finding the next Gleevec:FLT3 targeted kinase inhibitor therapy for acute myeloid leukemia.

Cancer Cell 1: 413–415

Scheffner M, Werness BA, Huibregtse JM et al. (1990) The E6 oncoprotein encoded by human papillomavirus

types 16 and 18 promotes the degradation of p53. Cell 63: 1129–1136

Scheijen B, Griffin JD (2002) Tyrosine kinase oncogenes in normal hematopoiesis and hematological disease.

Oncogene 21: 3314–3333

Schindler T, Bornmann W, Pellicena P et al. (2000) Structural mechanism for STI-571 inhibition of Abelson

tyrosine kinase. Science 289:1938–1942

Schlabach MR, Luo J, Solimini NL et al. (2008) Cancer proliferation gene discovery through functional genomics.

Science 319: 620‒624

Schmidt L, Duh FM, Chen F et al. (1997) Germline and somatic mutations in the tyrosine kinase domain of the

MET proto-oncogene in papillary renal carcinomas. Nature Genet 16: 68–73

Schnittger S, Schoch C, Dugas M et al. (2002) Analysis of FLT3 length mutations in 1003 patients with acute

myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and

usefulness as a marker for the detection of minimal disease. Blood 100: 59–66

Schröck E, du Manoir S, Veldman T et al. (1996) Multicolor spectral karyotyping of human chromosomes. Science

273: 494–497

Schulte JH, Horn S, Otto T et al. (2008) MYCN regulates oncogenic micro RNAs in neuroblastoma. Int. J. Cancer

122: 699‒704

Schwab M, Alitalo K, Klempnauer KH et al. (1983) Amplified DNA with limited homology to myc cellular oncogene

is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305: 245–248

Schwarz K, Gauss GH, Ludwig L et al. (1996) RAG mutations in human B cellnegative SCID. Science 274: 97–99

Sciacco M, Bonilla E, Schon EA et al. (1994) Distribution of wild-type and common deletion forms of mtDNA in

normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy. Hum Mol Genet 3:

13–19

Scott RH, Douglas J, Baskomb L et al. (2008) Constitutional 11p15 abnormalities, including heritable imprinting

center mutations, cause nonsyndromic Wilms tumor. Nat Genet 40: 1329-34

Seaman S, Stevens J, Yang MY et al. (2007) Genes that distinguish physiological and apthological angiogenesis.

Cancer Cell 11: 539‒554

Sebolt-Leopold JS, Dudley DT, Herrera R et al. (1999) Blockade of the MAP kinase pathway suppresses growth

of colon tumors in vivo. Nature Med 5: 810–816

Seeger RC, Brodeur GM, Sather H et al. (1985) Association of multiple copies of the N-myc oncogene with rapid

progression of neuroblastomas. N Engl J Med 313: 1111–1116

Selbach M, Schwanhäuser B, Thierfelder N et al. (2008) Widespread changes in protein synthesis induced by

microRNAs. Nature 455: 58‒63

Seligson DB, Horvath S, Shi T et al. (2005) Global histone modification patterns predict risk of prostate cancer

recurrence. Nature 435: 1262‒1266

Serrano M, Lin AW, McCurrach ME et al. (1997) Oncogenic ras provokes premature cell senescence associated

with accumulation of p53 and p16INK4a. Cell 88:593‒602

Sévenet N, Lellouch-Tubiana A, Schofield D et al. (1999) Spectrum of hSNF5/INI1 somatic mutations in human

cancer and genotype-phenotype correlations. Hum Mol Genet 8: 2359–2368

Shachaf C, Kopelman AM, Arvanistis C et al. (2004) MYC inactivation uncovers pluripotent differentiation and

tumour dormancy in hepatocellular cancer. Nature 431: 1112‒1117

Shadel GS, Clayton DA (1997) Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem 66: 409–435

Page 21: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Shapiro G, Harper JW (1999) Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest 104: 1645–

1653

Shaulian E, Karin M (2002) AP-1 as a regulator of cell life and death. Nature Cell Biol 4: E131‒E136

Shay JW, Zou Y, Hiyama E et al. (2001) Telomerase and cancer. Hum Mol Genet 10: 677–685

Shen JC, Loeb LA (2000) The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases.

Trends Genet 16: 213–220

Shen L, Toyota M, Kondo Y et al. (2007) Integrated genetic and epigenetic analysis identifies three different

subclasses of colon cancer. Proc. Natl. Acad. Sci. (USA) 104: 18654‒18659

Sherr CJ (2004) Principles of tumor suppression. Cell 116: 235‒246

Sherr CJ, Weber JD (2000) The ARF/p53 pathway. Curr Opin Genet Dev 10: 94–99

Shi B, Yaremko B, Hajian G et al (2000) The farnesyl protein transferase inhibitor SCH66336 synergizes with

taxanes in vitro and enhances their antitumor activity in vivo. Cancer Chemother Pharmacol 46: 387–93

Shih IM, Zhou W, Goodman SN et al. (2001) Evidence that genetic instability occurs at an early stage of

colorectal tumorigenesis. Cancer Res 61: 818–822

Shipp MA, Ross KN, Tamayo P et al. (200) Diffuse large B-cell lymphoma outcome prediction by gene-expression

profiling and supervised machine learning. Nature Med 8: 68–74

Shlien A, Tabori U, Marshall CR et al. (2008) Excessive genomic DNA copy number variation in the Li-Fraumeni

cancer predisposition syndrome. Proc. Natl. Acad. Sci. (USA) 105: 11264‒11269

Shyu AB, Wilkinson MF, van Hoof A (2008) Messenger RNA regulation: to translate or to degrade. EMBOJ 27:

471‒481

Side L, Taylor B, Cayouette M (1997) Homozygous inactivation of the NFI gene in bone marrow cells from

children with neurofibromatosis type 1 and malignant myeloid disorders. N Engl J Med 336: 1713–1717

Sidransky D (1997) Nucleic acid-based methods for the detection of cancer. Science 278: 1054–1058

Sidransky D (2002) Emerging molecular markers of cancer. Nature 2: 210–219

Sidransky D, Tokino T, Hamilton SR et al. (1992) Identification of ras oncogene mutations in the stool of patients

with curable colorectal tumors. Science 256: 102–105

Singh KK, Russell J, Sigala B et al. (1999) Mitochondrial DNA determines the cellular response to cancer

therapeutic agents. Oncogene 18: 6641–6646

Skorski T (2002) Oncogenic tyrosine kinases and the DNA-damage response. Nature Rev Cancer 2: 351–360

Slack A, Chen Z, Tonelli R et al. (2005) The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN

in neuroblastoma. Proc. Natl. Acad. Sci. (USA) 102: 731‒736

Slamon DJ, Clark GM, Wong SG et a. (1987) Human breast cancer: correlation of relapse and survival with

amplification of the HER-2/neu oncogene. Science 235: 177–182

Slamon DJ, Leyland-Jones B, Shak S et al. (2001) Use of chemotherapy plus a monoclonal antibody against

HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783–792

Slebos RJC, Kibbelaar RE, Dalesio O et al. (1990) K-RAS oncogene activation as a prognostic marker in

adenocarcinoma of the lung. N Engl J Med 323: 561–565

Smith G, Carey FA, Beattie J et al. (2002) Mutations in APC, Kirsten-ras, and p53‒alternative genetic pathways to

colorectal cancer. Proc Natl Acad Sci USA 99: 9433–9438

Smith LT, Otterson GA, Plass C (2007) Unraveling the epigenetic code of cancer for therapy. Trends Genet. 23:

449‒456

Soengas MS, Alaræon RM, Yoshida H et al. (1999) Apaf-1 and caspase-9 in p53-Dependent apoptosis and tumor

inhibition. Science 284: 156–158

Soengas MS, Capodieci P, Polsky D et al. (2001) Inactivation of the apoptosis effector Apaf-1 in malignant

melanoma. Nature 409: 207–211

Solé F, Espinet B, Sanz GF et al. (2000) Incidence, characterization and prognostic significance of chromosomal

abnormalities in 640 patients with primary myelodysplastic syndromes. Br J Haematol 108: 346–356

Solit DB, Garraway LA, Pratilas CA et al. (2006) BRAF mutation predicts sensitivity to MEK inhibition. Nature 439:

358‒362

Solomon SD, McMurray JJV, Pfeffer MA et al. (2005) Cardiovascular risk associated with celecoxib in a clinical

trial for colorectal adenoma prevention. N. Engl. J. Med. 352: 1071‒1080

Songyang Z, Carraway III KL, Eck MJ et al. (1995) Catalytic specificity of protein-tyrosine kinases is critical for

selective signalling. Nature 373: 536–539

Soong R, Grieu F, Robbins P (1997) p53 alterations are associated with improved prognosis in distal colonic

carcinomas. Clin Cancer Res 3: 1405–1411

Soussi T (1996) The p53 tumour suppressor gene: a model for molecular epidemiology of human cancer. Mol

Med Today 1: 32–37

Soussi T, Wiman KG (2007) Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer

Cell 12: 303‒312

Page 22: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Souza RF, Appel R, Yin J et al. (1996) Microsatellite instability in the insulinlike growth factor II receptor gene in

gastrointestinal tumours. Nature Genet 14: 255–257

Speicher MR, Ballard SG, Ward DC (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH.

Nature Genet 12: 368–375

Spruck CH, Won KA, Reed SI (1999) Deregulated cyclin E induces chromosome instability. Nature 40: 297–300

Stankovic T, Weber P, Stewart G et al. (1999) Inactivation of ataxia telangiectasia mutated gene in B-cell chronic

lymphocytic leukaemia. Lancet 353: 26–29

Stansel RM, de Lange T, Griffith JD (2001) T-loop assembly in vitro involves binding of TRF2 near the 3’

telomeric overhang. EMBO J 20: 5532–5540

Stark GR, Wahl GM (1984) Gene amplification. Ann Rev Biochem 53: 447–491

Staunton JE, Slonim DK, Coller HA et al. (2001) Chemosensitivity prediction by transcriptional profiling. Proc Natl

Acad Sci USA 98: 10787–10792

Steenman M, Westerveld A, Mannens M (2000) Genetics of Beckwith-Wiedemann syndrome-associated tumors:

common genetic pathways. Genes Chromosomes Cancer 28: 1–13

Steenman MJC, Rainier S, Dobry CJ et al. (1994) Loss of imprinting of IGF2 is linked to reduced expression and

abnormal methylation of H19 in Wilms’tumour. Nature Genet 7: 433–439

Stehelin D, Varmus HE, Bishop JM et al.(1976) DNA related to the transforming gene(s) of avian sarcoma viruses

is present in normal avian DNA. Nature 260:170–173

Steinbach G, Lynch PM, Phillips RK et al. (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial

adenomatous polyposis. N Engl J Med 342: 1946–1952

Stewart GS, Maser RS, Stankovic T et al. (1999) The DNA double-strand break repair gene hMRE11 is mutated

in individuals with an ataxiatelangiectasia-like disorder. Cell 99: 577–587

Stiewe T, Pützer BM (2000) Role of the p53‒homologue p73 in E2F1‒induced apoptosis. Nature Genet 26: 464–

469

Stilgenbauer S, Leupolt E, Ohl S et al. (1995) Heterogeneity of deletions involving RB-1 and the D13S25 locus in

B-cell chronic lymphocytic leukemia revealed by fluorescence in situ hybridization. Cancer Res 55: 3475–3477

Stilgenbauer S, Schaffner C, Litterst A et al. (1997) Biallelic mutations in the ATM gene in T-prolymphocytic

leukemia. Nature Med 3: 1155–1159

Storz G (2002) An expanding universe of noncoding RNAs. Science 296: 1260–1263

Stranger BE, Forrest MS, Dunning M et al. (2007) Relative impact of nucleotide and copy number variation on

gene expression phenotypes. Science 315: 848‒853

Stratton MR, Rahman N (2008) The emerging landscape of breast cancer susceptibility. Nature Genet. 40: 17‒22

Streubel B, Chott A, Huber D et al. (2004) Lymphoma-specific genetic alterations in microvascular endothelial

cells in B-cell lymphomas. N. Engl. J. Med. 351: 250‒259

Struewing JP, Hartge P, Wacholder S et al. (1997) The risk of cancer associated with specific mutations of

BRCA1 abd BRCA2 among Ashkenazi jews. N Engl J Med 336: 1401–1408

Su LK, Kinzler KW, Vogelstein B et al. (1992) Multiple intestinal neoplasia caused by a mutation in the murine

homolog of the APC gene. Science 256: 668–670

Su ZZ, Lebedeva IV, Gopalkrishnan RV et al. (2001) A combinatorial approach for selectively inducing

programmed cell death in human pancreatic cancer cells. Proc Natl Acad Sci USA 98: 10332–10337

Sukumar S, Notario V, Martin -Zanca D et al. (1983) Induction of mammary carcinomas in rats by nitroso-

methylurea involves malignant activation of H-ras-1 locus by single point mutations. Nature 306: 658–661

Suter CM, Martin DJK, Ward RL (2004) Germline epimutation of MLH1 in individuals with multiple cancers. Nature

Genet. 36: 497‒501

Sutherland GR, Richards RJ (1995) The molecular basis of fragile sites in human chromosomes. Curr Opin Genet

Dev 5: 323–327

Svejstrup JQ (2002) Mechanisms of transcription-coupled DNA repair. Nature Rev Mol Cell Biol 3: 21–29

Talpaz M, Silver RT, Druker BJ et al. (2002) Imatinib induces durable hematologic and cytogenetic responses in

patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 99: 1928–1937

Tanaka H, Arakawa H, Yamaguchi T et al. (2000) A ribonucleotide reductase gene involved in a p53-Dependent

cell-cycle checkpoint for DNA damage. Nature 404: 42–49

T’Ang A, Varley JM, Chakraborty S et al. (1988) Structural rearrangement of the retinoblastoma gene in human

breast carcinoma. Science 242: 263–266

Tang X, Zhu Y, Han L et al. (2007) CP-31398 restores mutant p53 tumor suppressor function and inhibits UVB-

induced skin carcinogenesis in mice. J. Clin. Invest. 117: 3753‒3764

Tao W, Levine AJ (1999) P19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad

Sci USA 96: 6937–6941

Taub R, Kirsch I, Morton C et al. (1982) Translocation of the c-myc gene into the immunoglobulin heavy chain

locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci USA 79: 7837–7841

Page 23: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Taub JW, Konrad MA, Ge Y et al. (2002) High frequency of leukemic clones in newborn screening blood samples

of children with B-precursor acute lymphoblastic leukemia. Blood 99: 2992–2996

Tavazoie S, Alarcon C, Oskarsson T et al. (2008) Endogenous human micro RNAs that suppress breast cancer

metastasis. Nature 451: 147‒152

Taylor JK, Zhang QQ, Wyatt JR et al. (1999) Induction of endogenous Bcl-xS through the control of Bcl-x pre-

mRNA splicing by antisense oligonucleotides. Nature Biotechnol 17: 1097–1100

Teitz T, Wei T, Valentine MB et al. (2000) Caspase 8 is deleted or silenced preferentially in childhood

neuroblastomas with amplification of MYCN. Nature Med 6: 529–535

Tetsu O, McCormick F (1999) -catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:

422–426

Thangavelu M, Olopade O, Beckman E et al. (1990) Clinical, morphologic, and cytogenetic characteristics of

patients with lymphoid malignancies characterized by both t (14;18)(q32;q21) and t (8;14)(q24;q32) or t

(8;22)(q24;q11). Genes Chromosomes Cancer 2: 147–158

The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C elegans: a platform for

investigating biology. Science 282: 2012–2018

The CHEK2‒Breast Cancer Consortium (2002) Low-penetrance susceptibility to breast cancer due to

CHEK2*1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nature Genet 31: 55–59

The FANTOM Consortium und RIKEN Genome Exploration Research Group and Genome Science Group (2005).

The transcriptional landscape of the mammalian genome. Science 309: 1559‒1563

The International Hap Map Consortium (2005) A haplotype map of the human genome. Nature 437: 1299‒1320

Therrien JP, Drouin R, Baril C et al. (1999) Human cells compromised for p53 function exhibit defective global

and transcription-coupled nucleotide excision repair, whereas cells compromised for pRb function are

defective only in global repair. Proc Natl Acad Sci USA 96: 15038–15043

Thiede C, Steudel C, Mohr B et al. (2002) Analysis of FLT3‒activating mutations in 979 patients with acute

myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.

Blood 99: 4326–4335

Thomas RK, Baker A, DeBiasi RM et al. (2007) High-throughput oncogene mutation profiling in human cancer.

Nature Genet. 39: 347‒351

Thorlacius S, Struewing JP, Hartge P et al. (1998) Population-based study of risk of breast cancer in carriers of

BRCA2 mutation. Lancet 352: 1337–1339

Threadgill DW (2005) Metastatic potential as a heritable trait. Nature Genet. 37: 1026‒1027

Tomlinson I, Sasieni P, Bodmer W (2002) How many mutations in cancer? Am J Pathol 160: 755–758

Tomlinson I, Webb E, Carvajal-Carmona L et al. (2007) A genome-wide association scan of tag SNPs identifies a

susceptibility variant for colorectal cancer at 8q24.21. Nature Genet. 39: 984‒988

Toyota M, Ahuja N, Ohe-Toyota M et al. (1999) CpG island methylator phenotype in colorectal cancer. Proc. Natl.

Acad. Sci USA 96: 8681–8686

Tsujii M, Kawano S, Tsujii S et al. (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells.

Cell 93: 705–716

Tutt A, Ashworth A (2002) The relationship between the roles of BRCA genes in DNA repair and cancer

predisposition. Trends Mol Med 8: 571–576

Tycko B (2000) Epigenetic gene silencing in cancer. J Clin Invest 105: 401–407

Ullrich A, Schlessinger J (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61: 203–212

Urano T, Emkey R, Feig LA (1996) Ral-GTPases mediate a distinct downstream signaling pathway from Ras that

facilitates cellular transformation. EMBO J 15: 810–816

Vafa O, Wade M, Kern S et al. (2002) c-Myc can induce DNA damage, increase reactive oxygen species, and

mitigate p53 function: a mechanism for oncogene-induced genetic instability. Mol Cell 9: 1031–1044

van de Vijver MJ, He YD, van’t Veer LJ (2002) A gene-expression signature as a predictor of survival in breast

cancer. N Engl J Med 347: 1999–2009

van Dongen JJM, Wolvers-Tettero ILM (1991a) Analysis of immunoglobulin and T cell receptor genes. Part I:

basic and technical aspects. Clin Chim Acta 198: 1–91

van Dongen JJM, Wolvers-Tettero ILM (1991b) Analysis of immunoglobulin and T cell receptor genes. Part II:

possibilities and limitations in the diagnosis and management of lymphoproliferative diseases and related

disorders. Clin Chim Acta 198: 93–174

van Dongen JJM, Seriu T, Panzer-Grümayer ER et al. (1998) Prognostic value of minimal residual disease in

acute lymphoblastic leukaemia in childhood. Lancet 352: 1731–1738

van Gool AJ, van der Horst GTJ, Citterio E et al. (1997) Cockayne syndrome: defective repair of transcription?

EMBO J 16: 4155–4162

van ‘t Veer LJ, Dai H, van de Vijver MJ et al. (2002) Gene expression profiling predicts clinical outcome of breast

cancer. Nature 415: 530–536

Page 24: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Varambally S, Cao Q, Mani RS et al. (2008) Genomic loss of microRNA-101 leads to overexpression of histone

methyltransferase EZH2 in cancer. Science 322: 1695-9

Varley H, Pickett HA, Foxon JL et al. (2002) Molecular characterization of intertelomere and intra-telomere

mutations in human ALT cells. Nature Genet 30: 301–305

Varon R, Vissinga C, Platzer M et al. (1998) Nibrin, a novel DNA doublestrand break repair protein, is mutated in

Nijmegen breakage syndrome. Cell 93: 467–476

Vaziri H, Dessain SK, Eaton EN et al. (2001) hSIR2SIRT1 functions as an NADdependent p53 deacetylase. Cell

107: 149–159

Ventura A, Kirsch DG, McLaughlin ME et al. (2007) Restoration of p53 function leads to tumour repression in vivo.

Nature 445: 661‒665

Versteege I, Sévenet N, Lange J et al. (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric

cancer. Nature 394: 203–206

Vetter IR, Wittinghofer A (2001) The guanine nucleotide-binding switch in three dimensions. Science 294: 1299–

1304

Virtaneva K, Wright FA, Tanner SM et al. (2001) Expression profiling reveals fundamental biological differences in

acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics. Proc Natl Acad Sci USA 98: 1124–

1129

Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3‒kinase-akt pathway in human cancer. Nature Rev

Cancer 2: 489–501

Vogelstein B, Kinzler KW (1992) p53 function and dysfunction. Cell 70: 523–526

Vogelstein B, Fearon ER, Hamilton SR et al. (1988) Genetic alterations during colorectal tumor development. N

Engl J Med 319: 525–532

Vogelstein B, Fearon ER, Kern SE et al. (1989) Allelotype of colorectal carcinomas. Science 244: 207–211

Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408: 307–310

von Bubnoff N, Schneller F, Peschel C et al.(2002) BCR-ABL gene mutations in relation to clinical resistance of

Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 359: 487–491

Vousden KH (2000) p53: death star. Cell 103: 691–694

Vousden KH, Lu X (2002) Live or let die: The cell’s response to p53. Nature Rev Cancer 2:594–604

Wadayama B, Toguchida J, Shimizu et al. (1994) Mutation spectrum of the retinoblastoma gene in

osteosarcomas. Cancer Res 54: 3042–3048

Walker JR, Corpina RA, Goldberg J (2001) Structure of the Ku heterodimer bound to DNA and its implications for

double-strand break repair. Nature 412: 607–614

Wang ET, Sandberg R, Luo S et al. (2009) Alternative isoform regulation in human tissue transcriptomes. Nature

456: 470-6

Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283: 1482–1488

Wang W (2007) Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA

proteins. Nature Rev. Genet. 8: 735‒748

Wang XW, Tseng A, Ellis NA et al. (2001) Functional interaction of p53 and BLM DNA helicase in apoptosis. J

Biol Chem 276: 32948–32955

Warburg O (1956) On the origin of cancer cells. Science 123: 309‒314

Weber RG, Boström J, Wolter M et al.(1997) Analysis of genomic alterations in benign, atypical, and anaplastic

meningiomas: toward a genetic model of meningioma progression. Proc Natl Acad Sci USA 94: 14719–14724

Weinstein JN, Myers TG, O’Connor PM et al. (1997) An information-intensive approach to the molecular

pharmacology of cancer. Science 275: 343–349

Weisberg E, Manley PW, Cowan-Jacob SW, Hochhaus A, Griffin JD (2007) Second generation inhibitors of BCR-

ABL for the treatment of imatinib-resistant chronic myeloid leukemia. Nature Rev. Cancer 7: 345‒356

Weischer M, Bojesen SE, Ellervik C et al. (2008) CHEK2* 1100delC genotyping for clinical assessment of breast

cancer risk: meta analyses of 26.000 patient cases and 27.000 controls. J. Clin. Oncol. 26: 542‒548

Weiss A, Schlessinger J (1998) Switching signals on or off by receptor dimerization. Cell 94: 277–280

Weiss WA, Aldape K, Mohapatra G et al. (1997) Targeted expression of MYCN causes neuroblastoma in

transgenic mice. EMBO J 16: 2985–2995

Weissman BE, Saxon PJ, Pasquale SR et al. (1987) Introduction of a normal human chromosome 11 into a

Wilms’ tumor cell line controls its tumorigenic expression. Science 236: 175–180

Wessendorf S, Fritz B, Wrobel G et al. (2002) Automated screening for genomic imbalances using matrix-based

comparative genomic hybridization. Lab Invest 82: 47–60

Wheeler DA, Srinivasan M, Egholm M et al. (2008) The complete genome of an individual by massively parallel

DNA sequencing. Nature 452: 872-6

Wiemels JL, Cazzaniga G, Daniotti M et al. (1999) Prenatal origin of acute lymphoblastic leukaemia in children.

Lancet 354: 1499–1503

Page 25: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Wiemels JL, Greaves M (1999) Structure and possible mechanisms of TELAML1 gene fusions in childhood acute

lymphoblastic leukemia. Cancer Res 59: 4075–4082

Willis TG, Dyer MJS (2000) The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies.

Blood 96: 808–822

Wilson JF, Weale ME, Smith AC et al. (2001) Population genetic structure of variable drug response. Nature

Genet 29: 265–269

Windle B, Draper BW, Yin YX et al. (1991) A central role for chromosome breakage in gene amplification, deletion

formation, and amplicon integration. Genes Dev 5: 160–174

Wolf U (1995) The genetic contribution to the phenotype. Hum Genet 95: 127–148

Wolf U (1997) Identical mutations and phenotypic variation. Hum Genet 100: 305–321

Wood LD, Parsons DW, Jones S et al. (2007) The genomic lanscapes of human breast and colorectal cancers.

Science 318: 1108‒1113

Wood RD, Mitchell M, Sgouros J et l. (2001) Human DNA repair genes. Science 291: 1284–1289

Wooster R (2000) Cancer classification with DNA microarrays is less more? Trends Genet 16: 327–329

Wu K-J, Grandori C, Amacker M et al. (1999) Direct activation of TERT transcription by c-MYC. Nature Genet. 21:

220–224

Wu X, Pandolfi PP (2001) Mouse models for multistepp tumorigenesis. Trends Cell Biol 11: 52–59

Xin H, Liu D, Wan M et al. (2007) TPP1 is a homologue of ciliate TEBP- β and interacts with POT1 to recruit

telomerase. Nature 445: 559‒562

Xu B, Kim ST, Kastan MB (2001) Involvement of Brca1 in S-phase and G2‒phase checkpoints after ionizing

irradiation. Mol Cell Biol 21: 3445–3450

Xu GF, O’Connell P, Viskochil D et al. (1990) The neurofibromatosis type 1 gene encodes a protein related to

GAP. Cell 63: 835–841

Xue W, Zender L, Miething C et al. (2007) Senescence and tumour clearance is triggered by p53 restoration in

murine liver carcinomas. Nature 445: 656‒660

Yamanishi Y, Boyle DL, Rosengren S et al. (2002) Regional analysis of p53 mutations in rheumatoid arthritis

synovium. Proc Natl Acad Sci USA 99: 10025–10030

Yan H, Dobbie Z, Gruber SB (2002) Small changes in expression affect predisposition to tumorigenesis. Nature

Genet 30: 25–26

Yanagisawa A, Ohtake K, Ohashi K et al. (1993) Frequent c-Ki-ras oncogene activation in mucous cell

hyperplasias of pancreas suffering from chronic inflammation. Cancer Res 53: 953–956

Yanaihara N, Caplen N, Bowman E et al. (2006) Unique micro RNA molecular profiles in lung cancer diagnosis

and prognosis. Cancer Cell 9: 189‒198

Yang A, McKeon F (2000) p63 and p73: p53 mimics, menaces and more. Nature Rev Mol Cell Biol 1: 199–207

Yang E, Korsmeyer SJ (1996) Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood 88:

386–401

Yano T, Sander CA, Clark HM et al. (1993) Clustered mutations in the second exon of the MYC gene in sporadic

Burkitt’s lymphoma. Oncogene 8: 2741–2748

Yarden RJ, Brody LC (1999) BRCA1 interacts with components of the histone deacetylase complex. Proc Natl

Acad Sci USA 96: 4983–4988

Yin Y, Tainsky MA, Bischoff FZ et al. (1992) Wild-type p53 restores cell cycle control and inhibits gene

amplification in cells with mutant p53 alleles. Cell 70: 937–948

Yoshimizu T, Miroglio A, Ripoche MA et al. (2008) The H19 locus acts in vivo as a tumor suppressor

Yoshiura K, Kanai Y, Ochiai A et al. (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG

methylation in human carcinomas. Proc Natl Acad Sci USA 92: 7416–7419

You M, Candrian U, Maronpot RR et al. (1989) Activation of the Ki-ras protooncogene in spontaneously occurring

and chemically induced lung tumors of the strain A mouse. Proc Natl Acad Sci USA 86: 3070–3074

Young KH, Leroy K, Mǿller MB et al. (2008) Structural profiles of TP53 gene mutations predict clinical outcome in

diffuse large B-cell lymphoma: an international collaborative study. Blood 112: 3088-98

Yu J, Hu S, Wang J et al. (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. indica). Science 296:

79–92

Yu J, Zhang L, Hwang PM et al. (1999) Identification and classification of p53‒regulated genes. Proc Natl Acad

Sci USA 96: 14517–14522

Yu J, Zhang L, Hwang PM et al. (2001a) PUMA induces the rapid apoptosis of colorectal cancer cells. Mol Cell 7:

673–682

Yu Q, Geng Y, Sicinski P (2001b) Specific protection against breast cancers by cyclin D1 ablation. Nature 411:

1017–1021

Zacchi P, Gostissa M, Uchida T et al. (2002) The prolyl isomerase Pin1 reveals a mechanism to control p53

functions after genotoxic insults. Nature 419: 853–857

Page 26: Kapitel 4: Genetische Grundlagen der Kanzerogenesestatic.springer.com/sgw/documents/1438405/application/pdf/Kap4... · Bird AP, Wolffe AP (1999) Methylation-induced repression –

Zang KD, Singer H (1967) Chromosomal constitution of meningiomas. Nature 216: 84–85

Zhang Y, Mukhopadhyay T, Donehower LA et al. (1993) Retroviral vectormediated transduction of K-ras

antisense RNA into human lung cancer cells inhibits expression of the malignant phenotype. Hum Gene Ther

4: 451–460

Zhang Y, Xiong Y, Yarbrough WG (1998) ARF promotes MDM 2 degradation and stabilizes p53: ARF-INK4a

locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92: 725–734

Zhang Z, Wang Y, Vikis HG et al. (2001) Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nature Genet

29: 25–33

Zheng H, You H, Zhou XZ et al. (2002) The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response.

Nature 419: 849–853

Zhong Q, Chen CF, Li S et al. (1999) Association of BRCA1 with the hRad50‒hMre11‒p95 complex and the DNA

damage response. Science 285: 747–750

Zhou ZQ, Hurlin PJ (2001) The interplay between Mad and Myc in proliferation and differentiation. Trends Cell

Biol 11: S10‒S14

Zuber J, Tchernitsa OI, Hinzmann B et al. (2000) A genome-wide survey of RAS transformation targets. Nature

Genet 24: 144–152