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Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas
Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict som...
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/PMC5677944/ https://www.ncbi.nlm.nih.gov/pubmed/29263839 http://dx.doi.org/10.1038/s41525-017-0032-5 |
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author | Madubata, Chioma J Roshan-Ghias, Alireza Chu, Timothy Resnick, Samuel Zhao, Junfei Arnes, Luis Wang, Jiguang Rabadan, Raul |
author_facet | Madubata, Chioma J Roshan-Ghias, Alireza Chu, Timothy Resnick, Samuel Zhao, Junfei Arnes, Luis Wang, Jiguang Rabadan, Raul |
author_sort | Madubata, Chioma J |
collection | PubMed |
description | Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict somatic variants from tumor-only samples and (2) identify somatic-like germline variants for integrated analysis of tumor-normal DNA. Using data from 1769 patients from seven cancer types (bladder, glioblastoma, low-grade glioma, lung, melanoma, stomach, and pediatric glioma), we show that “somatic-like” germline variants are enriched for autosomal-dominant cancer-predisposition genes (p < 4.35 × 10(−15)), including TP53. Our framework identifies germline and somatic nonsense variants in BRCA2 and other Fanconi anemia genes in 11% (11/100) of bladder cancer cases, suggesting a potential genetic predisposition in these patients. The bladder carcinoma patients with Fanconi anemia nonsense variants display a BRCA-deficiency somatic mutation signature, suggesting treatment targeted to DNA repair. |
format | Online Article Text |
id | pubmed-5677944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56779442017-12-20 Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas Madubata, Chioma J Roshan-Ghias, Alireza Chu, Timothy Resnick, Samuel Zhao, Junfei Arnes, Luis Wang, Jiguang Rabadan, Raul NPJ Genom Med Article Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict somatic variants from tumor-only samples and (2) identify somatic-like germline variants for integrated analysis of tumor-normal DNA. Using data from 1769 patients from seven cancer types (bladder, glioblastoma, low-grade glioma, lung, melanoma, stomach, and pediatric glioma), we show that “somatic-like” germline variants are enriched for autosomal-dominant cancer-predisposition genes (p < 4.35 × 10(−15)), including TP53. Our framework identifies germline and somatic nonsense variants in BRCA2 and other Fanconi anemia genes in 11% (11/100) of bladder cancer cases, suggesting a potential genetic predisposition in these patients. The bladder carcinoma patients with Fanconi anemia nonsense variants display a BRCA-deficiency somatic mutation signature, suggesting treatment targeted to DNA repair. Nature Publishing Group UK 2017-10-03 /pmc/articles/PMC5677944/ /pubmed/29263839 http://dx.doi.org/10.1038/s41525-017-0032-5 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 | Article Madubata, Chioma J Roshan-Ghias, Alireza Chu, Timothy Resnick, Samuel Zhao, Junfei Arnes, Luis Wang, Jiguang Rabadan, Raul Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title | Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title_full | Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title_fullStr | Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title_full_unstemmed | Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title_short | Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas |
title_sort | identification of potentially oncogenic alterations from tumor-only samples reveals fanconi anemia pathway mutations in bladder carcinomas |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677944/ https://www.ncbi.nlm.nih.gov/pubmed/29263839 http://dx.doi.org/10.1038/s41525-017-0032-5 |
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