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Functional germline variants as potential co-oncogenes
Germline variants that affect the expression or function of proteins contribute to phenotypic variation in humans and likely determine individual characteristics and susceptibility to diseases including cancer. A number of high penetrance germline variants that increase cancer risk have been identif...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700137/ https://www.ncbi.nlm.nih.gov/pubmed/29177190 http://dx.doi.org/10.1038/s41523-017-0051-5 |
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author | Agarwal, Divyansh Nowak, Christoph Zhang, Nancy R. Pusztai, Lajos Hatzis, Christos |
author_facet | Agarwal, Divyansh Nowak, Christoph Zhang, Nancy R. Pusztai, Lajos Hatzis, Christos |
author_sort | Agarwal, Divyansh |
collection | PubMed |
description | Germline variants that affect the expression or function of proteins contribute to phenotypic variation in humans and likely determine individual characteristics and susceptibility to diseases including cancer. A number of high penetrance germline variants that increase cancer risk have been identified and studied, but germline functional polymorphisms are not typically considered in the context of cancer biology, where the focus is primarily on somatic mutations. Yet, there is evidence from familial cancers indicating that specific cancer subtypes tend to arise in carriers of high-risk germline variants (e.g., triple negative breast cancers in mutated BRCA carriers), which suggests that pre-existing germline variants may determine which complementary somatic driver mutations are needed to drive tumorigenesis. Recent genome sequencing studies of large breast cancer cohorts reported only a handful of highly recurrent driver mutations, suggesting that different oncogenic events drive individual cancers. Here, we propose that germline polymorphisms can function as oncogenic modifiers, or co-oncogenes, and these determine what complementary subsequent somatic events are required for full malignant transformation. Therefore, we propose that germline aberrations should be considered together with somatic mutations to determine what genes drive cancer and how they may be targeted. |
format | Online Article Text |
id | pubmed-5700137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57001372017-11-24 Functional germline variants as potential co-oncogenes Agarwal, Divyansh Nowak, Christoph Zhang, Nancy R. Pusztai, Lajos Hatzis, Christos NPJ Breast Cancer Perspective Germline variants that affect the expression or function of proteins contribute to phenotypic variation in humans and likely determine individual characteristics and susceptibility to diseases including cancer. A number of high penetrance germline variants that increase cancer risk have been identified and studied, but germline functional polymorphisms are not typically considered in the context of cancer biology, where the focus is primarily on somatic mutations. Yet, there is evidence from familial cancers indicating that specific cancer subtypes tend to arise in carriers of high-risk germline variants (e.g., triple negative breast cancers in mutated BRCA carriers), which suggests that pre-existing germline variants may determine which complementary somatic driver mutations are needed to drive tumorigenesis. Recent genome sequencing studies of large breast cancer cohorts reported only a handful of highly recurrent driver mutations, suggesting that different oncogenic events drive individual cancers. Here, we propose that germline polymorphisms can function as oncogenic modifiers, or co-oncogenes, and these determine what complementary subsequent somatic events are required for full malignant transformation. Therefore, we propose that germline aberrations should be considered together with somatic mutations to determine what genes drive cancer and how they may be targeted. Nature Publishing Group UK 2017-11-22 /pmc/articles/PMC5700137/ /pubmed/29177190 http://dx.doi.org/10.1038/s41523-017-0051-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Perspective Agarwal, Divyansh Nowak, Christoph Zhang, Nancy R. Pusztai, Lajos Hatzis, Christos Functional germline variants as potential co-oncogenes |
title | Functional germline variants as potential co-oncogenes |
title_full | Functional germline variants as potential co-oncogenes |
title_fullStr | Functional germline variants as potential co-oncogenes |
title_full_unstemmed | Functional germline variants as potential co-oncogenes |
title_short | Functional germline variants as potential co-oncogenes |
title_sort | functional germline variants as potential co-oncogenes |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700137/ https://www.ncbi.nlm.nih.gov/pubmed/29177190 http://dx.doi.org/10.1038/s41523-017-0051-5 |
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