gene expression profiling for the investigation of soft tissue

REVIEW AND PERSPECTIVE Gene expression profiling for the investigation of soft tissue sarcoma pathogenesis and the identification of diagnostic, prognostic, and predictive biomarkers Andrew H. Beck & Robert B. West & Matt van de Rijn Received: 8 December 2008 /Revised: 31 March 2009 /Accepted: 14 April 2009 # Springer-V erlag 2009 Abstract Sof t tiss ue sarc omas are mali gna nt neoplas ms derived from mesenchymal tissues. Their pathogenesis is poorly unders tood and the re are few eff ecti ve treatme nt opti ons for advanced di sease. In the past decade, gene expres sion profil ing has bee n applied to sarcomas to fac ilita te und erst anding of sar coma pat hogene sis and to identify diagnostic, prognostic, and predictive markers. In this paper, we review this body of work and discuss how gene expression profiling has led to advancements in the unders tandin g of sarcoma patho biology , the identif ication of cli nic all y usefu l bio mar kers, and the ref ineme nt of sarcoma classifica tion schemes. Lastly, we conclu de with a discussion of strategies to further optimize the translation of gene exp ress ion dat a int o a gre ater unders tanding of sarcoma pathogenesis and improved clinical outcomes for sarcoma patien ts. Keywords Gene express ion profili ng . Microarrays . Genomics . Bioinformatics . Tumo r biolog y . Sof t tiss ue tumors . Sarcomas . Biomarkers . Molecu lar patho logy . Surgic al patho logy Introduction Sarcomas are malignant neoplasms derived from mesenchymal tissues. They represent a pproximately 1% of malignancies diagnosed annually. Sarcomas are currently diagnosed based on histopathological evaluation supplemented with the use of immuno histoch emistry and molecu lar diagn ostic techni ques in selected cases [ 1]. There are ~100 recognized histopathological subtypes of soft tissue tumors [2]. The rarity of these tumo rs and the lar ge number of diag nos tic ent itie s mak e sarcomas a challenging area of investigation. Cur rently , trea tme nt for sar coma s consis ts of sur ger y with consid eration for chemoth erapy and radioth erapy . The growing importance of comprehensive treatment regimens involving neoadjuvant chemotherapy [3] and preoperative radiotherapy [4] emphasi zes the importan ce of patho logical ana lysi s of pre ope rati ve biopsy mat eria l. The str ongest predictor of patient outcome is stage at time of diagnosis. Tr eatment opt ions are limited and few effective adj uva nt ther api es exist for advance d di sease. Due to the poor prog nosis and limited effective therapeutic options avail- able for most sarcomas, there is a major clinical need for increased understanding of sarcoma pathogenesis to facil- ita te the developme nt of new dia gno sti c mar kers and therapeutic agents [5, 6]. Gene expression microarray technology was developed in the mid- 1990s to per mit genome -wid e mon itor ing of gene expressi on [7 – 9]. The principal types of array platforms used for gene expression monitoring involve the robotic deposition of DNA fragments onto a glass slide [ 7] or the in situ synthesis of oligonucleotides on high-density arrays using photolithography [10]. Each of these technol- ogi es is abl e to produc e gen ome -wide mea surements of exp ression to produc e a “sna p sho t ” of a tumor ’s gene expression at a specific point in time. Virchows Arch DOI 10.1007/s00428-009-0774-2 A. H. Beck : R. B. West : M. van de Rijn ( *) Pathology Department, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305, USA e-mail: [email protected] R. B. West Pathology and Laboratory Service, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, USA

gene expression profiling for the investigation of soft tissue

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