Combinatorial patterns of somatic gene mutations in cancer

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Abstract
Cancer is a complex process in which the abnormalities of many genes appear to be involved. The combinatorial patterns of gene mutations may reveal the functional relations between genes and pathways in tumorigenesis as well as identify targets for treatment. We examined the patterns of somatic mutations of cancers from Catalog of Somatic Mutations in Cancer (COSMIC), a large-scale database curated by the Wellcome Trust Sanger Institute. The frequently mutated genes are well-known oncogenes and tumor suppressors that are involved in generic processes of cell-cycle control, signal transduction, and stress responses. These “signatures” of gene mutations are heterogeneous when the cancers from different tissues are compared. Mutations in genes functioning in different pathways can occur in the same cancer (i.e., co-occur), whereas those in genes functioning in the same pathway are rarely mutated in the same sample. This observation supports the view of tumorigenesis as derived from a process like Darwinian e...