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Identifying Epistasis in Cancer Genomes: A Delicate Affair.

ABSTRACT: Recent studies of the tumor genome seek to identify cancer pathways as groups of genes in which mutations are epistatic with one another or, specifically, "mutually exclusive." Here, we show that most mutations are mutually exclusive not due to pathway structure but to interactions with disease subtype and tumor mutation load. In particular, many cancer driver genes are mutated preferentially in tumors with few mutations overall, causing mutations in these cancer genes to appear mutually exclusive with numerous others. Researchers should view current epistasis maps with caution until we better understand the multiple cause-and-effect relationships among factors such as tumor subtype, positive selection for mutations, and gross tumor characteristics including mutational signatures and load.

SUBMITTER: van de Haar J

PROVIDER: S-EPMC6816465 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Identifying Epistasis in Cancer Genomes: A Delicate Affair.

van de Haar Joris J Canisius Sander S Yu Michael K MK Voest Emile E EE Wessels Lodewyk F A LFA Ideker Trey T

Cell 20190501 6

Recent studies of the tumor genome seek to identify cancer pathways as groups of genes in which mutations are epistatic with one another or, specifically, "mutually exclusive." Here, we show that most mutations are mutually exclusive not due to pathway structure but to interactions with disease subtype and tumor mutation load. In particular, many cancer driver genes are mutated preferentially in tumors with few mutations overall, causing mutations in these cancer genes to appear mutually exclusi ...[more]

PMID: 31150618

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