Rare, functional, somatic variants in gene families linked to cancer genes: GPCR signaling as a paradigm.

ABSTRACT: Oncodriver genes are usually identified when mutations recur in multiple tumours. Different drivers often converge in the activation or repression of key cancer-relevant pathways. However, as many pathways contain multiple members of the same gene family, individual mutations might be overlooked, as each family member would necessarily have a lower mutation frequency and thus not identified as significant in any one-gene-at-a-time analysis. Here, we looked for mutated, functional sequence positions in gene families that were mutually exclusive (in patients) with another gene in the same pathway, which identified both known and new candidate oncodrivers. For instance, many inactivating mutations in multiple G-protein (particularly G_i/o) coupled receptors, are mutually exclusive w

SUBMITTER: Raimondi F 

PROVIDER: S-EPMC6756116 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature