Abstract 5062: Integrated analysis of the whole exome sequencing (WES) identifies novel mutations and suggests patient selection hypothesis

Abstract

Abstract Whole exome sequencing was done on 257 breast and 102 ovarian tumors using next generation sequencing. Seven gigabases of sequencing data were generated for each sample or 100x coverage of the whole exome, which enable to determine sequence variations with >99% confidence. The results of the mutation calls were compared with recently published TCGA breast and ovarian datasets. Genes with large number of passenger mutations were called out and frequency of passenger mutations per sample was linked to MMR signature. In ovarian tumors, a high prevalence of p53 and BRCA1 mutation was confirmed in serous tumors. A signature of BRCA1/2 deficient tumors was developed and cross-validated between the datasets. In no-serous tumors, a high prevalence of mutations MAPK pathway and beta-catenin pathway were found. FOXL2 mutation was identified in 100% of granulose ovarian tumors and linked to high levels of EMT signature. In addition we showed a significant overlap between genes found to be mutated in TCGA datasets and in our dataset, suggesting a larger number of potentially significantly mutated genes than previously reported. In breast tumors, known high frequency of mutations was confirmed in PIK3CA and TP53 genes and validated with respective pathway specific gene expression signatures. In addition, prevalent mutations were identified in MAPK and PI3K pathways and linked with respective pathway signatures. These findings strengthen and enrich our understanding of molecular subtypes of ovarian and breast tumors and can be used for identification of novel targets and for development of responder hypothesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5062. doi:1538-7445.AM2012-5062