Association between germline variants and somatic mutations in colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease with evidence of distinct tumor types that develop through different somatically altered pathways. To better understand the impact of the host genome on somatically mutated genes and pathways, we assessed associations of germline variations with som...

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Autores: Barfield, Richard, Qu, Conghui, Steinfelder, Robert S., Zeng, Chenjie, Harrison, Tabitha A., Brezina, Stefanie, Buchanan, Daniel D., Campbell, Peter T., Casey, Graham, Gallinger, Steven, Giannakis, Marios, Gruber, Stephen B., Gsur, Andrea, Hsu, Li, Huyghe, Jeroen R., Moreno Aguado, Víctor, Newcomb, Polly A., Ogino, Shuji, Phipps, Amanda I., Slattery, Martha L., Thibodeau, Stephen N., Trinh, Quang M., Toland, Amanda E., Hudson, Thomas J., Sun, Wei, Zaidi, Syed H., Peters, Ulrike
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/187816
Acceso en línea:https://hdl.handle.net/2445/187816
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Polimorfisme genètic
Colorectal cancer
Genetic polymorphisms
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spelling Association between germline variants and somatic mutations in colorectal cancerBarfield, RichardQu, ConghuiSteinfelder, Robert S.Zeng, ChenjieHarrison, Tabitha A.Brezina, StefanieBuchanan, Daniel D.Campbell, Peter T.Casey, GrahamGallinger, StevenGiannakis, MariosGruber, Stephen B.Gsur, AndreaHsu, LiHuyghe, Jeroen R.Moreno Aguado, VíctorNewcomb, Polly A.Ogino, ShujiPhipps, Amanda I.Slattery, Martha L.Thibodeau, Stephen N.Trinh, Quang M.Toland, Amanda E.Hudson, Thomas J.Sun, WeiZaidi, Syed H.Peters, UlrikeCàncer colorectalPolimorfisme genèticColorectal cancerGenetic polymorphismsColorectal cancer (CRC) is a heterogeneous disease with evidence of distinct tumor types that develop through different somatically altered pathways. To better understand the impact of the host genome on somatically mutated genes and pathways, we assessed associations of germline variations with somatic events via two complementary approaches. We first analyzed the association between individual germline genetic variants and the presence of non-silent somatic mutations in genes in 1375 CRC cases with genome-wide SNPs data and a tumor sequencing panel targeting 205 genes. In the second analysis, we tested if germline variants located within previously identified regions of somatic allelic imbalance were associated with overall CRC risk using summary statistics from a recent large scale GWAS (n similar or equal to 125 k CRC cases and controls). The first analysis revealed that a variant (rs78963230) located within a CNA region associated with TLR3 was also associated with a non-silent mutation within gene FBXW7. In the secondary analysis, the variant rs2302274 located in CDX1/PDGFRB frequently gained/lost in colorectal tumors was associated with overall CRC risk (OR = 0.96, p = 7.50e-7). In summary, we demonstrate that an integrative analysis of somatic and germline variation can lead to new insights about CRC.Springer Science and Business Media LLC2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/187816Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-022-14408-2Scientific Reports, 2022, vol. 12, num. 1, p. 10207https://doi.org/10.1038/s41598-022-14408-2cc by (c) Barfield, Richard et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1878162026-05-27T06:46:51Z
dc.title.none.fl_str_mv Association between germline variants and somatic mutations in colorectal cancer
title Association between germline variants and somatic mutations in colorectal cancer
spellingShingle Association between germline variants and somatic mutations in colorectal cancer
Barfield, Richard
Càncer colorectal
Polimorfisme genètic
Colorectal cancer
Genetic polymorphisms
title_short Association between germline variants and somatic mutations in colorectal cancer
title_full Association between germline variants and somatic mutations in colorectal cancer
title_fullStr Association between germline variants and somatic mutations in colorectal cancer
title_full_unstemmed Association between germline variants and somatic mutations in colorectal cancer
title_sort Association between germline variants and somatic mutations in colorectal cancer
dc.creator.none.fl_str_mv Barfield, Richard
Qu, Conghui
Steinfelder, Robert S.
Zeng, Chenjie
Harrison, Tabitha A.
Brezina, Stefanie
Buchanan, Daniel D.
Campbell, Peter T.
Casey, Graham
Gallinger, Steven
Giannakis, Marios
Gruber, Stephen B.
Gsur, Andrea
Hsu, Li
Huyghe, Jeroen R.
Moreno Aguado, Víctor
Newcomb, Polly A.
Ogino, Shuji
Phipps, Amanda I.
Slattery, Martha L.
Thibodeau, Stephen N.
Trinh, Quang M.
Toland, Amanda E.
Hudson, Thomas J.
Sun, Wei
Zaidi, Syed H.
Peters, Ulrike
author Barfield, Richard
author_facet Barfield, Richard
Qu, Conghui
Steinfelder, Robert S.
Zeng, Chenjie
Harrison, Tabitha A.
Brezina, Stefanie
Buchanan, Daniel D.
Campbell, Peter T.
Casey, Graham
Gallinger, Steven
Giannakis, Marios
Gruber, Stephen B.
Gsur, Andrea
Hsu, Li
Huyghe, Jeroen R.
Moreno Aguado, Víctor
Newcomb, Polly A.
Ogino, Shuji
Phipps, Amanda I.
Slattery, Martha L.
Thibodeau, Stephen N.
Trinh, Quang M.
Toland, Amanda E.
Hudson, Thomas J.
Sun, Wei
Zaidi, Syed H.
Peters, Ulrike
author_role author
author2 Qu, Conghui
Steinfelder, Robert S.
Zeng, Chenjie
Harrison, Tabitha A.
Brezina, Stefanie
Buchanan, Daniel D.
Campbell, Peter T.
Casey, Graham
Gallinger, Steven
Giannakis, Marios
Gruber, Stephen B.
Gsur, Andrea
Hsu, Li
Huyghe, Jeroen R.
Moreno Aguado, Víctor
Newcomb, Polly A.
Ogino, Shuji
Phipps, Amanda I.
Slattery, Martha L.
Thibodeau, Stephen N.
Trinh, Quang M.
Toland, Amanda E.
Hudson, Thomas J.
Sun, Wei
Zaidi, Syed H.
Peters, Ulrike
author2_role author
author
author
author
author
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 Càncer colorectal
Polimorfisme genètic
Colorectal cancer
Genetic polymorphisms
topic Càncer colorectal
Polimorfisme genètic
Colorectal cancer
Genetic polymorphisms
description Colorectal cancer (CRC) is a heterogeneous disease with evidence of distinct tumor types that develop through different somatically altered pathways. To better understand the impact of the host genome on somatically mutated genes and pathways, we assessed associations of germline variations with somatic events via two complementary approaches. We first analyzed the association between individual germline genetic variants and the presence of non-silent somatic mutations in genes in 1375 CRC cases with genome-wide SNPs data and a tumor sequencing panel targeting 205 genes. In the second analysis, we tested if germline variants located within previously identified regions of somatic allelic imbalance were associated with overall CRC risk using summary statistics from a recent large scale GWAS (n similar or equal to 125 k CRC cases and controls). The first analysis revealed that a variant (rs78963230) located within a CNA region associated with TLR3 was also associated with a non-silent mutation within gene FBXW7. In the secondary analysis, the variant rs2302274 located in CDX1/PDGFRB frequently gained/lost in colorectal tumors was associated with overall CRC risk (OR = 0.96, p = 7.50e-7). In summary, we demonstrate that an integrative analysis of somatic and germline variation can lead to new insights about CRC.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/187816
url https://hdl.handle.net/2445/187816
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41598-022-14408-2
Scientific Reports, 2022, vol. 12, num. 1, p. 10207
https://doi.org/10.1038/s41598-022-14408-2
dc.rights.none.fl_str_mv cc by (c) Barfield, Richard et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Barfield, Richard et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Science and Business Media LLC
publisher.none.fl_str_mv Springer Science and Business Media LLC
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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