Abstract LB-239: Mutational and clonal analyses across TCGA cancer types using the MuSiC suite of tools.

Within the field of cancer genomics, advances in next-generation sequencing and variant detection methods have tremendously reduced the costs of generating genomic data for large cohorts of patients in translational cancer research. These large datasets have enabled statistical analyses of somatic events in tumor-normal pairs, with the ultimate goal of understanding the molecular mechanisms underlying various cancer phenotypes. Here, we present results from the suite of tools collectively called MuSiC (Mutational Significance in Cancer), specifically designed towards this goal. Somatic alterations of more than 5000 tumors across 20 cancer types are now publicly available as part of The Cancer Genome Atlas (TCGA). This includes point mutations and small indels from exome sequencing, copy-number variants from SNP arrays, and gene and allele-specific expression from mRNA sequencing. We present results from the suite that integrates these data types to identify significantly altered genes, gene families, protein domains, and pathways. Also presented are the distribution of mutation types, frequencies, and patterns across cancer types, or across histological subtypes of tumors. Further, we identify mutations that can distinguish broader expression and/or methylation subtypes and clinically relevant phenotypes across the combined pan-cancer data set. Finally, we perform clonality analysis across several cancer types by integrating copy number data to identify important mutations that drive the development of new clones. Citation Format: Cyriac Kandoth, Michael D. McLellan, Christopher A. Miller, Charles Lu, Nathan Dees, Kai Ye, Beifang Niu, Michael C. Wendl, Richard K. Wilson, Li Ding. Mutational and clonal analyses across TCGA cancer types using the MuSiC suite of tools. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-239. doi:10.1158/1538-7445.AM2013-LB-239