Work

3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets

Year: 2017

Type: article

Abstract: Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy.

Source: Genome Medicine

DOI: 10.1186/s13073-016-0393-x

Authors: Jianjiong Gao, Matthew T. Chang, Hannah C. Johnsen, Sizhi Paul Gao, Brooke E. Sylvester, Selcuk Onur Sumer, Hongxin Zhang, David B. Solit, Barry S. Taylor, Nikolaus Schultz, Chris Sander

Institutions: Memorial Sloan Kettering Cancer Center, University of California, San Francisco, Cornell University, Weill Cornell Medicine, Harvard University, Dana-Farber Cancer Institute

Language: English

Topic: Cancer Genomics and Diagnostics

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,290

Funders: Prostate Cancer Foundation, Sontag Foundation, Robertson Foundation, Cycle for Survival, National Institutes of Health, Marie-Josée and Henry R. Kravis Center for Molecular Oncology, National Cancer Institute

Awards: Understanding Long Tail Driver Mutations in Cancer, G1901299981, G4102770861, G5109122429, G5181012032, G5711250986, G7136384868, G9000003249, G9000048103, Cancer Center Support Grant

OpenAlex ID: W2582236637

FWCI: 7.53

Cites: 46

Cited by: 219

Related to: 10