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Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors
Alterations in DNA repair pathways are common in tumors and can result in characteristic mutational signatures; however, a specific mutational signature associated with somatic alterations in the nucleotide excision repair (NER) pathway has not yet been identified. Here, we examine the mutational pr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936490/ https://www.ncbi.nlm.nih.gov/pubmed/27111033 http://dx.doi.org/10.1038/ng.3557 |
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author | Kim, Jaegil Mouw, Kent W Polak, Paz Braunstein, Lior Z Kamburov, Atanas Kwiatkowski, David J Rosenberg, Jonathan E Van Allen, Eliezer M D'Andrea, Alan Getz, Gad |
author_facet | Kim, Jaegil Mouw, Kent W Polak, Paz Braunstein, Lior Z Kamburov, Atanas Kwiatkowski, David J Rosenberg, Jonathan E Van Allen, Eliezer M D'Andrea, Alan Getz, Gad |
author_sort | Kim, Jaegil |
collection | PubMed |
description | Alterations in DNA repair pathways are common in tumors and can result in characteristic mutational signatures; however, a specific mutational signature associated with somatic alterations in the nucleotide excision repair (NER) pathway has not yet been identified. Here, we examine the mutational processes operating in urothelial cancer, a tumor type in which the core NER gene ERCC2 is significantly mutated. Analysis of three independent urothelial tumor cohorts reveals a strong association between somatic ERCC2 mutations and activity of a mutational signature characterized by a broad spectrum of base changes. In addition, we note an association between activity of this signature and smoking that is independent of ERCC2 mutation status, providing genomic evidence of tobacco-related mutagenesis in urothelial cancer. Together, these analyses identify the first NER-related mutational signature and highlight the related roles of DNA damage and subsequent DNA repair in shaping the tumor mutational landscape. |
format | Online Article Text |
id | pubmed-4936490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-49364902016-10-25 Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors Kim, Jaegil Mouw, Kent W Polak, Paz Braunstein, Lior Z Kamburov, Atanas Kwiatkowski, David J Rosenberg, Jonathan E Van Allen, Eliezer M D'Andrea, Alan Getz, Gad Nat Genet Article Alterations in DNA repair pathways are common in tumors and can result in characteristic mutational signatures; however, a specific mutational signature associated with somatic alterations in the nucleotide excision repair (NER) pathway has not yet been identified. Here, we examine the mutational processes operating in urothelial cancer, a tumor type in which the core NER gene ERCC2 is significantly mutated. Analysis of three independent urothelial tumor cohorts reveals a strong association between somatic ERCC2 mutations and activity of a mutational signature characterized by a broad spectrum of base changes. In addition, we note an association between activity of this signature and smoking that is independent of ERCC2 mutation status, providing genomic evidence of tobacco-related mutagenesis in urothelial cancer. Together, these analyses identify the first NER-related mutational signature and highlight the related roles of DNA damage and subsequent DNA repair in shaping the tumor mutational landscape. 2016-04-25 2016-06 /pmc/articles/PMC4936490/ /pubmed/27111033 http://dx.doi.org/10.1038/ng.3557 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kim, Jaegil Mouw, Kent W Polak, Paz Braunstein, Lior Z Kamburov, Atanas Kwiatkowski, David J Rosenberg, Jonathan E Van Allen, Eliezer M D'Andrea, Alan Getz, Gad Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title | Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title_full | Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title_fullStr | Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title_full_unstemmed | Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title_short | Somatic ERCC2 Mutations Are Associated with a Distinct Genomic Signature in Urothelial Tumors |
title_sort | somatic ercc2 mutations are associated with a distinct genomic signature in urothelial tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936490/ https://www.ncbi.nlm.nih.gov/pubmed/27111033 http://dx.doi.org/10.1038/ng.3557 |
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