Expression of kinase genes in primary Expression of kinase genes in primary hyperparathyroidism;hyperparathyroidism;Adenoma versus hyperplastic parathyroid Adenoma versus hyperplastic parathyroid tissuetissue

Pinhas P. Schachter1 M.D., Suhail Ayesh2 PhD, Tamar Schneider2,

Morris Laster M.D., Abraham Czerniak1 M.D. and Abraham Hochberg2

BackgroundBackground

Differentiation between parathyroid hyperplasia and adenoma is difficult and based on the surgeon’s skill. Microarrays and other sophisticated research tools generate information about differential gene expression in various tissues.

Exploration of genes that express differentially in one tissue will enable identification and perhaps development of new methods of preoperative or intraoperative diagnosis.

MethodsMethods

• RNA was extracted from parathyroid hyperplasia and adenoma tissue and hybridized to a microarray containing 359 human cDNAs of known kinase genes.

• Signals of exposure were scanned and quantified with Atlas – Image, version 2, software for digital image analysis. The program generates a color schematic comparison view and numerical data in a tabular format for further analysis.

Expression of kinase genes In Adenoma Expression of kinase genes In Adenoma Parathyroid TissueParathyroid Tissue

Expression of kinase genes In hyperplasia Parathyroid Expression of kinase genes In hyperplasia Parathyroid TissueTissue

The first row data format in text modeThe first row data format in text mode

The second excel format of dataThe second excel format of data

The third access format after classeficationThe third access format after classefication

Table 1 Genes expressed in Parathyroid hyperplasia onlyTable 1 Genes expressed in Parathyroid hyperplasia only

Table 2 Genes expressed in Parathyroid adenoma onlyTable 2 Genes expressed in Parathyroid adenoma only

Table 3 Genes up regulated in Parathyroid adenomaTable 3 Genes up regulated in Parathyroid adenoma

Table 4 Genes down regulated in Parathyroid adenomaTable 4 Genes down regulated in Parathyroid adenoma

Table 5 Genes categories by functionTable 5 Genes categories by function

ConclusionConclusion

The ratio values that are considered significant (<0.5 or >1.5) suggest that genes up-regulated in parathyroid adenoma are those responsible for angiogenesis and production of blood vessels. Genes down-regulated in parathyroid adenoma and expressed in hyperplasia are related to a decrease in apoptosis. Moreover, an interesting gene expressed only in the hyperplasia sample is increased in relation to in vivo proliferation activities

http://research.dfci.harvard.edu/korsmeyer/MLL.htmhttp://research.dfci.harvard.edu/korsmeyer/MLL.htm

• MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia Scott A. Armstrong1–4, Jane E. Staunton5, Lewis B.

Silverman1,3,4, Rob Pieters6, Monique L. den Boer6, Mark

D. Minden7, Stephen E. Sallan1,3,4, Eric S. Lander5, Todd R. Golub1,3,4,5* & Stanley J. Korsmeyer2,4,8*

*These authors contributed equally to this work.

AbstractAbstract• Acute lymphoblastic leukemias carrying a chromosomal translocation

involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes.

Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias.

We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia.

Establishing that MLL is a unique entity is critical, as it mandates the examination of

selectively expressed genes for urgently needed molecular targets.

Genes that distinguish ALL from MLL. The 100 genes that Genes that distinguish ALL from MLL. The 100 genes that are most highly correlated with the class distinctionare most highly correlated with the class distinction

Selected early lymphocyte gene expression in ALL and Selected early lymphocyte gene expression in ALL and MLLMLL

Selected HOX gene expression in ALL and MLLSelected HOX gene expression in ALL and MLL

Comparison of gene expression between ALL, Mll and AML Comparison of gene expression between ALL, Mll and AML

ALL (red), MLL (blue), AML (yellow)ALL (red), MLL (blue), AML (yellow)

Genes that are specifically expressed in MLL, ALL or MLLGenes that are specifically expressed in MLL, ALL or MLL

Classification of ALL, MLL and AML on the basis of their gene Classification of ALL, MLL and AML on the basis of their gene expression profile. The error rate in class prediction (y axis) is plotted expression profile. The error rate in class prediction (y axis) is plotted

against the number of genes used to build the model (x axis).against the number of genes used to build the model (x axis).