Abstract
Abstract The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. The ever-expanding sequencing capacity ushered in by the second generation of DNA sequencers has enabled complete base-level description of the cancer genome and is therefore deepening our understanding of the etiology of the disease. We have combined a variety of approaches centered on next generation sequencing technologies aimed at comprehensive characterization of the cancer genome to define the key molecular lesions that drive tumor initiation and progression. These include targeted exonic sequencing to define coding sequence mutation, whole genome shotgun sequencing to define structural rearrangements, and cDNA sequencing to define alteration in expression levels, aberrant splicing and fusion transcripts. We have applied these approaches to pancreatic adenocarcinoma, hepatocellualr carcinoma and colorectal carcinoma. Results of genome sequencing have yielded an unprecedented picture of the rearrangements and mutations from analysis of read sequence and read coverage across the chromosomes. Evident in both the cancers is a dramatic reduction in SNP variation in the tumor genome compared to the germline from the same individual owing to extensive loss of heterozygosity. Superimposed on this are a few thousand mutations, some of which drive the tumor phenotype. The corresponding set of analog data generated by SNP-array microarray platforms provide validation of the central results from sequencing which leads to a new appreciation of the relationship between genetic change and the malignant phenotype. 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 2218.
Published Version
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