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3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets
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 cluste...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260099/ https://www.ncbi.nlm.nih.gov/pubmed/28115009 http://dx.doi.org/10.1186/s13073-016-0393-x |
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author | Gao, Jianjiong Chang, Matthew T. Johnsen, Hannah C. Gao, Sizhi Paul Sylvester, Brooke E. Sumer, Selcuk Onur Zhang, Hongxin Solit, David B. Taylor, Barry S. Schultz, Nikolaus Sander, Chris |
author_facet | Gao, Jianjiong Chang, Matthew T. Johnsen, Hannah C. Gao, Sizhi Paul Sylvester, Brooke E. Sumer, Selcuk Onur Zhang, Hongxin Solit, David B. Taylor, Barry S. Schultz, Nikolaus Sander, Chris |
author_sort | Gao, Jianjiong |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-016-0393-x) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5260099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-52600992017-01-26 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets Gao, Jianjiong Chang, Matthew T. Johnsen, Hannah C. Gao, Sizhi Paul Sylvester, Brooke E. Sumer, Selcuk Onur Zhang, Hongxin Solit, David B. Taylor, Barry S. Schultz, Nikolaus Sander, Chris Genome Med Method 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-016-0393-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-23 /pmc/articles/PMC5260099/ /pubmed/28115009 http://dx.doi.org/10.1186/s13073-016-0393-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Method Gao, Jianjiong Chang, Matthew T. Johnsen, Hannah C. Gao, Sizhi Paul Sylvester, Brooke E. Sumer, Selcuk Onur Zhang, Hongxin Solit, David B. Taylor, Barry S. Schultz, Nikolaus Sander, Chris 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title | 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title_full | 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title_fullStr | 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title_full_unstemmed | 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title_short | 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
title_sort | 3d clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets |
topic | Method |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260099/ https://www.ncbi.nlm.nih.gov/pubmed/28115009 http://dx.doi.org/10.1186/s13073-016-0393-x |
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