Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutatio...

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Autores: Wang, Shengfeng, Pitt, Jason J., Zheng, Yonglan, Yoshimatsu, Toshio F., Gao, Guimin, Sanni, Ayodele, Oluwasola, Olayiwola, Ajani, Mustapha, Fitzgerald, Dominic, Odetunde, Abayomi, Khramtsova, Galina, Hurley, Ian, Popoola, Abiodun, Falusi, Adeyinka, Ogundiran, Temidayo, Obafunwa, John, Ojengbede, Oladosu, Ibrahim, Nasiru, Barretina, Jordi, White, Kevin P., Huo, Dezheng, Olopade, Olufunmilayo I.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/18296
Acceso en línea:http://hdl.handle.net/10256/18296
Access Level:acceso abierto
Palabra clave:Mama -- Càncer
Breast -- Cancer
Polimorfisme genètic
Genetic polymorphisms
Mutació (Biologia)
Mutation (Biology)
Mutagènesi
Mutagenesis
Mama -- Càncer -- Aspectes genètics
Mama -- Cancer -- Genetic aspects
Epigenètica
Epigenetics
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spelling Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and NigeriaWang, ShengfengPitt, Jason J.Zheng, YonglanYoshimatsu, Toshio F.Gao, GuiminSanni, AyodeleOluwasola, OlayiwolaAjani, MustaphaFitzgerald, DominicOdetunde, AbayomiKhramtsova, GalinaHurley, IanPopoola, AbiodunFalusi, AdeyinkaOgundiran, TemidayoObafunwa, JohnOjengbede, OladosuIbrahim, NasiruBarretina, JordiWhite, Kevin P.Huo, DezhengOlopade, Olufunmilayo I.Mama -- CàncerBreast -- CancerPolimorfisme genèticGenetic polymorphismsMutació (Biologia)Mutation (Biology)MutagènesiMutagenesisMama -- Càncer -- Aspectes genèticsMama -- Cancer -- Genetic aspectsEpigenèticaEpigeneticsSomatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole‐genome or whole‐exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60–85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h 2 = 0.575, p = 0.010) and the combined APOBEC signatures (h 2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21–0.45) of APOBEC signature contribution at genome‐wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10−6). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesisWiley2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/18296http://hdl.handle.net/10256/18296International Journal of Cancer, 2019, vol. 145, núm. 12, p. 3321-3333Articles publicats (IdIBGi)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.32498info:eu-repo/semantics/altIdentifier/issn/0020-7136info:eu-repo/semantics/altIdentifier/eissn/1097-0215Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/182962026-05-29T05:05:01Z
dc.title.none.fl_str_mv Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
title Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
spellingShingle Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
Wang, Shengfeng
Mama -- Càncer
Breast -- Cancer
Polimorfisme genètic
Genetic polymorphisms
Mutació (Biologia)
Mutation (Biology)
Mutagènesi
Mutagenesis
Mama -- Càncer -- Aspectes genètics
Mama -- Cancer -- Genetic aspects
Epigenètica
Epigenetics
title_short Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
title_full Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
title_fullStr Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
title_full_unstemmed Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
title_sort Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria
dc.creator.none.fl_str_mv Wang, Shengfeng
Pitt, Jason J.
Zheng, Yonglan
Yoshimatsu, Toshio F.
Gao, Guimin
Sanni, Ayodele
Oluwasola, Olayiwola
Ajani, Mustapha
Fitzgerald, Dominic
Odetunde, Abayomi
Khramtsova, Galina
Hurley, Ian
Popoola, Abiodun
Falusi, Adeyinka
Ogundiran, Temidayo
Obafunwa, John
Ojengbede, Oladosu
Ibrahim, Nasiru
Barretina, Jordi
White, Kevin P.
Huo, Dezheng
Olopade, Olufunmilayo I.
author Wang, Shengfeng
author_facet Wang, Shengfeng
Pitt, Jason J.
Zheng, Yonglan
Yoshimatsu, Toshio F.
Gao, Guimin
Sanni, Ayodele
Oluwasola, Olayiwola
Ajani, Mustapha
Fitzgerald, Dominic
Odetunde, Abayomi
Khramtsova, Galina
Hurley, Ian
Popoola, Abiodun
Falusi, Adeyinka
Ogundiran, Temidayo
Obafunwa, John
Ojengbede, Oladosu
Ibrahim, Nasiru
Barretina, Jordi
White, Kevin P.
Huo, Dezheng
Olopade, Olufunmilayo I.
author_role author
author2 Pitt, Jason J.
Zheng, Yonglan
Yoshimatsu, Toshio F.
Gao, Guimin
Sanni, Ayodele
Oluwasola, Olayiwola
Ajani, Mustapha
Fitzgerald, Dominic
Odetunde, Abayomi
Khramtsova, Galina
Hurley, Ian
Popoola, Abiodun
Falusi, Adeyinka
Ogundiran, Temidayo
Obafunwa, John
Ojengbede, Oladosu
Ibrahim, Nasiru
Barretina, Jordi
White, Kevin P.
Huo, Dezheng
Olopade, Olufunmilayo I.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Mama -- Càncer
Breast -- Cancer
Polimorfisme genètic
Genetic polymorphisms
Mutació (Biologia)
Mutation (Biology)
Mutagènesi
Mutagenesis
Mama -- Càncer -- Aspectes genètics
Mama -- Cancer -- Genetic aspects
Epigenètica
Epigenetics
topic Mama -- Càncer
Breast -- Cancer
Polimorfisme genètic
Genetic polymorphisms
Mutació (Biologia)
Mutation (Biology)
Mutagènesi
Mutagenesis
Mama -- Càncer -- Aspectes genètics
Mama -- Cancer -- Genetic aspects
Epigenètica
Epigenetics
description Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole‐genome or whole‐exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60–85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h 2 = 0.575, p = 0.010) and the combined APOBEC signatures (h 2 = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21–0.45) of APOBEC signature contribution at genome‐wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10−6). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/18296
http://hdl.handle.net/10256/18296
url http://hdl.handle.net/10256/18296
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/ijc.32498
info:eu-repo/semantics/altIdentifier/issn/0020-7136
info:eu-repo/semantics/altIdentifier/eissn/1097-0215
dc.rights.none.fl_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv International Journal of Cancer, 2019, vol. 145, núm. 12, p. 3321-3333
Articles publicats (IdIBGi)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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