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Systematic identification of mutations and copy number alterations associated with cancer patient prognosis
Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almo...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289580/ https://www.ncbi.nlm.nih.gov/pubmed/30526857 http://dx.doi.org/10.7554/eLife.39217 |
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author | Smith, Joan C Sheltzer, Jason M |
author_facet | Smith, Joan C Sheltzer, Jason M |
author_sort | Smith, Joan C |
collection | PubMed |
description | Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almost all cancer driver genes contain remarkably little information on patient prognosis. However, CNAs in these same driver genes harbor significant prognostic power. Focal CNAs are associated with worse outcomes than broad alterations, and CNAs in many driver genes remain prognostic when controlling for stage, grade, TP53 status, and total aneuploidy. By performing a meta-analysis across independent patient cohorts, we identify robust prognostic biomarkers in specific cancer types, and we demonstrate that a subset of these alterations also confer specific therapeutic vulnerabilities. In total, our analysis establishes a comprehensive resource for cancer biomarker identification and underscores the importance of gene copy number profiling in assessing clinical risk. |
format | Online Article Text |
id | pubmed-6289580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-62895802018-12-12 Systematic identification of mutations and copy number alterations associated with cancer patient prognosis Smith, Joan C Sheltzer, Jason M eLife Cancer Biology Successful treatment decisions in cancer depend on the accurate assessment of patient risk. To improve our understanding of the molecular alterations that underlie deadly malignancies, we analyzed the genomic profiles of 17,879 tumors from patients with known outcomes. We find that mutations in almost all cancer driver genes contain remarkably little information on patient prognosis. However, CNAs in these same driver genes harbor significant prognostic power. Focal CNAs are associated with worse outcomes than broad alterations, and CNAs in many driver genes remain prognostic when controlling for stage, grade, TP53 status, and total aneuploidy. By performing a meta-analysis across independent patient cohorts, we identify robust prognostic biomarkers in specific cancer types, and we demonstrate that a subset of these alterations also confer specific therapeutic vulnerabilities. In total, our analysis establishes a comprehensive resource for cancer biomarker identification and underscores the importance of gene copy number profiling in assessing clinical risk. eLife Sciences Publications, Ltd 2018-12-11 /pmc/articles/PMC6289580/ /pubmed/30526857 http://dx.doi.org/10.7554/eLife.39217 Text en © 2018, Smith and Sheltzer http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cancer Biology Smith, Joan C Sheltzer, Jason M Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title | Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title_full | Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title_fullStr | Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title_full_unstemmed | Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title_short | Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
title_sort | systematic identification of mutations and copy number alterations associated with cancer patient prognosis |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289580/ https://www.ncbi.nlm.nih.gov/pubmed/30526857 http://dx.doi.org/10.7554/eLife.39217 |
work_keys_str_mv | AT smithjoanc systematicidentificationofmutationsandcopynumberalterationsassociatedwithcancerpatientprognosis AT sheltzerjasonm systematicidentificationofmutationsandcopynumberalterationsassociatedwithcancerpatientprognosis |