Title |
3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets
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Published in |
Genome Medicine, January 2017
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DOI | 10.1186/s13073-016-0393-x |
Pubmed ID | |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 43 | 46% |
United Kingdom | 7 | 7% |
Australia | 3 | 3% |
Spain | 3 | 3% |
Singapore | 2 | 2% |
Italy | 2 | 2% |
Montenegro | 1 | 1% |
Belgium | 1 | 1% |
Austria | 1 | 1% |
Other | 5 | 5% |
Unknown | 26 | 28% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 48 | 51% |
Members of the public | 40 | 43% |
Science communicators (journalists, bloggers, editors) | 3 | 3% |
Practitioners (doctors, other healthcare professionals) | 3 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | <1% |
United Kingdom | 1 | <1% |
Sweden | 1 | <1% |
Australia | 1 | <1% |
Unknown | 207 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 53 | 25% |
Researcher | 42 | 20% |
Student > Master | 23 | 11% |
Student > Bachelor | 18 | 8% |
Other | 15 | 7% |
Other | 30 | 14% |
Unknown | 31 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 68 | 32% |
Agricultural and Biological Sciences | 48 | 23% |
Medicine and Dentistry | 19 | 9% |
Computer Science | 15 | 7% |
Nursing and Health Professions | 4 | 2% |
Other | 20 | 9% |
Unknown | 38 | 18% |