Abstract 3934: Identification of novel cancer DNA sequence variants in human sarcomas

Abstract

Abstract Understanding of the genetic basis of cancer initiation and progression is a fundamental goal of cancer research. Identification of cancer variants is of profound importance for both understanding disease mechanism and for developing novel therapies. Soft-tissue sarcomas are multiple uncommon histotypes with features of diverse connective tissue lineages. Although some of their underlying genetic changes have been elucidated, for example in those types which contain etiologic chromosome translocations, in general, the genetics of these tumors is incompletely described. Adult soft tissue sarcomas often exhibit highly complex genomic rearrangements. To search for novel variants in these tumors, we utilized a custom “targeted-resequencing” approach to sequence coding exons from over 1300 known cancer-related genes and candidate gene families in 65 soft-tissue sarcoma patient samples covering several subtypes and their matching normal tissues where available. We used the previously published method of “In-solution capture” to enrich for regions of interest and sequenced both the normals and the tumors using the Illumina GAII platform. The variant calls reveal the distribution of mutations affecting the exons of the targeted regions across histotypes, and reveal the role of critical functional pathways in sarcoma genesis. Preliminary data suggest that TP53 single nucleotide variants are mostly confined to one histotype. This work is an important step in cataloging novel cancer mutations in these cancers, with potential implications for understanding their biology and the development of new therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3934. doi:10.1158/1538-7445.AM2011-3934