Open AccessRecurrent high-impact mutations at cognate structural positions in class A G protein-coupled receptors expressed in tumors
Author(s) -
Eunna Huh,
Jonathan Gallion,
Melina A. Agosto,
Sara J. Wright,
Theodore G. Wensel,
Olivier Lichtarge
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2113373118
Subject(s) - g protein coupled receptor , biology , effector , receptor , genetics , computational biology , mutation , signal transduction , phenotype , gene , microbiology and biotechnology
Significance GPCRs and GPCR pathways are increasingly being implicated in human malignancies, placing them among the most promising cancer drug candidates. Our results reveal enrichment of highly impactful, recurrent GPCR mutations within cancers. We found that cognate mutations in selected class A GPCRs have deleterious effects on signaling function. The results also suggest that olfactory receptors, often considered inconsequential, display a nonrandom mutation pattern in tumors in which they are expressed. These findings support the idea that protein paralogs can act in parallel as members of an onco-group.