Abstract 1139: Complete characterization of prostate cancer genomes by massively parallel sequencing

Abstract

Abstract Prostate cancer is the most common type of cancer diagnosed among men in the United States, accounting for 200,000 new cases and 27,000 deaths per year. Prior genetic studies have shown that chromosomal rearrangements comprise a major mechanism of oncogene activation in prostate cancer. For example, androgen-regulated gene fusions involving ETS family transcription factors are present in the majority of prostate cancers, yet the full repertoire of genomic alterations driving prostate carcinogenesis and progression remains unknown. Toward this end, recent technological advances have made it possible to characterize the full complement of somatic mutations in a single tumor through whole genome sequencing. We are using massively parallel sequencing technology to characterize the complete genomes of several primary prostate adenocarcinomas at >30x coverage. All samples are high-grade primary tumors (Gleason grade 7 to 9) and include cases with and without known ETS family translocations. For each tumor, we are also obtaining >30x sequence coverage of matched normal DNA from blood of these same patients in order to determine the somatic component of the overall variation we observe. Our results indicate that translocations and other chromosomal rearrangements occur frequently in prostate cancer, at a rate of >100 per genome. Further, we have discovered many nonsynonymous sequence mutations (point mutations and indels) in each tumor, some of which may represent novel candidate drivers of tumor progression. The overall rate of somatic point mutations is approximately 1 per Megabase. Integrated analysis of all genomes reveals both recurrent and private alterations. Together, these results illuminate potential avenues for target discovery and demonstrate the unparalleled value in performing complete genome sequencing in this malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1139.