A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies

Abstract Single nucleotide variants (SNVs) identified in cancer genomes can be de-convolved using non-negative matrix factorization (NMF) into discrete trinucleotide-based mutational signatures indicative of specific cancer-causing processes. The stability of NMF-generated mutational signatures depe...

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Autores principales:	Philip R. Davidson, Amy L. Sherborne, Barry Taylor, Alice O. Nakamura, Jean L. Nakamura
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18916e3fad1b4077bd253d4b9366ceb3
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spelling	oai:doaj.org-article:18916e3fad1b4077bd253d4b9366ceb32021-12-02T16:07:56ZA pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies10.1038/s41598-017-07888-02045-2322https://doaj.org/article/18916e3fad1b4077bd253d4b9366ceb32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07888-0https://doaj.org/toc/2045-2322Abstract Single nucleotide variants (SNVs) identified in cancer genomes can be de-convolved using non-negative matrix factorization (NMF) into discrete trinucleotide-based mutational signatures indicative of specific cancer-causing processes. The stability of NMF-generated mutational signatures depends upon the numbers of variants available for analysis. In this work, we sought to assess whether data from well-controlled mouse models can compensate for scarce human data for some cancer types. High quality sequencing data from radiotherapy-induced cancers is particularly scarce and the mutational processes defining ionizing radiation (IR)-induced mutagenesis in vivo are poorly defined. Here, we combine sequencing data from mouse models of IR-induced malignancies and human IR-induced malignancies. To determine whether the signatures identified from IR-exposed subjects can be differentiated from other mutagenic signatures, we included data from an ultraviolet radiation (UV)-induced human skin cancer and from a mouse model of urethane-induced cancers. NMF distinguished all three mutagens and in the pooled analysis IR was associated with mutational signatures common to both species. These findings illustrate the utility of pooled analysis of mouse and human sequencing data.Philip R. DavidsonAmy L. SherborneBarry TaylorAlice O. NakamuraJean L. NakamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Philip R. Davidson Amy L. Sherborne Barry Taylor Alice O. Nakamura Jean L. Nakamura A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
description	Abstract Single nucleotide variants (SNVs) identified in cancer genomes can be de-convolved using non-negative matrix factorization (NMF) into discrete trinucleotide-based mutational signatures indicative of specific cancer-causing processes. The stability of NMF-generated mutational signatures depends upon the numbers of variants available for analysis. In this work, we sought to assess whether data from well-controlled mouse models can compensate for scarce human data for some cancer types. High quality sequencing data from radiotherapy-induced cancers is particularly scarce and the mutational processes defining ionizing radiation (IR)-induced mutagenesis in vivo are poorly defined. Here, we combine sequencing data from mouse models of IR-induced malignancies and human IR-induced malignancies. To determine whether the signatures identified from IR-exposed subjects can be differentiated from other mutagenic signatures, we included data from an ultraviolet radiation (UV)-induced human skin cancer and from a mouse model of urethane-induced cancers. NMF distinguished all three mutagens and in the pooled analysis IR was associated with mutational signatures common to both species. These findings illustrate the utility of pooled analysis of mouse and human sequencing data.
format	article
author	Philip R. Davidson Amy L. Sherborne Barry Taylor Alice O. Nakamura Jean L. Nakamura
author_facet	Philip R. Davidson Amy L. Sherborne Barry Taylor Alice O. Nakamura Jean L. Nakamura
author_sort	Philip R. Davidson
title	A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
title_short	A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
title_full	A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
title_fullStr	A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
title_full_unstemmed	A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
title_sort	pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/18916e3fad1b4077bd253d4b9366ceb3
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A pooled mutational analysis identifies ionizing radiation-associated mutational signatures conserved between mouse and human malignancies

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