Integrative analysis of a cancer somatic mutome

Abstract

Background: The consecutive acquisition of genetic alterations characterizes neoplastic processes. As a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. The recent identification of the collection of somatically mutated genes in breast tumors (breast cancer somatic 'mutome') allows the comprehensive study of its function and organization in complex networks. Results: We analyzed functional genomic data (loss of heterozygosity, copy number variation and gene expression in breast tumors) and protein binary interactions from public repositories to identify potential novel components of neoplastic processes, the functional relationships between them, and to examine their coordinated function in breast cancer pathogenesis. This analysis identified candidate tumor suppressors and oncogenes, and new genes whose expression level predicts survival rate in breast cancer patients. Mutome network modeling using different types of pathological and healthy functional relationships unveils functional modules significantly enriched in genes or proteins (genes/proteins) with related biological process Gene Ontology terms and containing known breast cancer-related genes/proteins. Conclusion: This study presents a comprehensive analysis of the breast somatic mutome, highlighting those genes with a higher probability of playing a determinant role in tumorigenesis and better defining molecular interactions related to the neoplastic process.

MAP would like to offer his personal thanks to Marc Vidal, for introducing him to and developing his knowledge of the world of complex systems. This work was supported by the Fundació la Caixa (grant BM05-254-00 awarded to MAP), the Catalan Institute of Oncology (PH), the Instituto de Salud Carlos III (RCESP-C03/09 and RTICCC-C03/10) and SAF2003/5821. MAP is a Ramón y Cajal Researcher with the Spanish Ministry of Education and Science.