Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2020 |
| País: | España |
| Recursos: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositório: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/173462 |
| Acesso em linha: | https://hdl.handle.net/2445/173462 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Càncer colorectal Carcinogènesi Colorectal cancer Carcinogenesis |
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survivalZaidi, Syed H.Harrison, Tabitha A.Phipps, Amanda I.Steinfelder, Robert S.Trinh, Quang M.Qu, ConghuiBanbury, Barbara L.Georgeson, PeterGrasso, Catherine S.Giannakis, MariosAdams, Jeremy B.Alwers, ElizabethAmitay, Efrat L.Barfield, Richard T.Berndt, Sonja I.Borozan, IvanBrenner, HermannBrezina, StefanieBuchanan, Daniel D.Cao, YinChan, Andrew T.Chang-Claude, JennyConnolly, Charles M.Drew, David A.Farris III, Alton BradFigueiredo, Jane C.French, Amy J.Fuchs, Charles S.Garraway, Levi A.Gruber, SteveGuinter, Mark A.Hamilton, Stanley R.Harlid, SophiaHeisler, Lawrence E.Hidaka, AkihisaHopper, John L.Huang, Wen-YiHuyghe, Jeroen R.Jenkins, Mark A.Krzyzanowski, Paul M.Lemire, MathieuLin, YiLuo, XuemeiMardis, Elaine R.McPherson, John D.Miller, Jessica K.Moreno Aguado, VíctorMu, Xinmeng JasmineNishihara, ReikoPapadopoulos, Nikolaos G.Pasternack, DanielleQuist, Michael J.Rafikova, AdilyaReid, Emma E. G.Shinbrot, EveShirts, Brian H.Stein, Lincoln D.Teney, Cherie D.Timms, LeeUm, Caroline Y.Van Guelpen, BethanyVan Tassel, MeganWang, XiaolongWheeler, David A.Yung, Christina K.Hsu, LiOgino, ShujiGsur, AndreaNewcomb, Polly A.Gallinger, StevenHoffmeister, MichaelCampbell, Peter T.Thibodeau, Stephen N.Sun, WeiHudson, Thomas J.Peters, UlrikeCàncer colorectalCarcinogènesiColorectal cancerCarcinogenesisColorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.Nature Publishing Group2021202120202021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfhttps://hdl.handle.net/2445/173462Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-020-17386-zNature Communications, 2020, vol. 11https://doi.org/10.1038/s41467-020-17386-zcc by (c) Zaidi et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1734622026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| title |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| spellingShingle |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival Zaidi, Syed H. Càncer colorectal Carcinogènesi Colorectal cancer Carcinogenesis |
| title_short |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| title_full |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| title_fullStr |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| title_full_unstemmed |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| title_sort |
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival |
| dc.creator.none.fl_str_mv |
Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert S. Trinh, Quang M. Qu, Conghui Banbury, Barbara L. Georgeson, Peter Grasso, Catherine S. Giannakis, Marios Adams, Jeremy B. Alwers, Elizabeth Amitay, Efrat L. Barfield, Richard T. Berndt, Sonja I. Borozan, Ivan Brenner, Hermann Brezina, Stefanie Buchanan, Daniel D. Cao, Yin Chan, Andrew T. Chang-Claude, Jenny Connolly, Charles M. Drew, David A. Farris III, Alton Brad Figueiredo, Jane C. French, Amy J. Fuchs, Charles S. Garraway, Levi A. Gruber, Steve Guinter, Mark A. Hamilton, Stanley R. Harlid, Sophia Heisler, Lawrence E. Hidaka, Akihisa Hopper, John L. Huang, Wen-Yi Huyghe, Jeroen R. Jenkins, Mark A. Krzyzanowski, Paul M. Lemire, Mathieu Lin, Yi Luo, Xuemei Mardis, Elaine R. McPherson, John D. Miller, Jessica K. Moreno Aguado, Víctor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nikolaos G. Pasternack, Danielle Quist, Michael J. Rafikova, Adilya Reid, Emma E. G. Shinbrot, Eve Shirts, Brian H. Stein, Lincoln D. Teney, Cherie D. Timms, Lee Um, Caroline Y. Van Guelpen, Bethany Van Tassel, Megan Wang, Xiaolong Wheeler, David A. Yung, Christina K. Hsu, Li Ogino, Shuji Gsur, Andrea Newcomb, Polly A. Gallinger, Steven Hoffmeister, Michael Campbell, Peter T. Thibodeau, Stephen N. Sun, Wei Hudson, Thomas J. Peters, Ulrike |
| author |
Zaidi, Syed H. |
| author_facet |
Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert S. Trinh, Quang M. Qu, Conghui Banbury, Barbara L. Georgeson, Peter Grasso, Catherine S. Giannakis, Marios Adams, Jeremy B. Alwers, Elizabeth Amitay, Efrat L. Barfield, Richard T. Berndt, Sonja I. Borozan, Ivan Brenner, Hermann Brezina, Stefanie Buchanan, Daniel D. Cao, Yin Chan, Andrew T. Chang-Claude, Jenny Connolly, Charles M. Drew, David A. Farris III, Alton Brad Figueiredo, Jane C. French, Amy J. Fuchs, Charles S. Garraway, Levi A. Gruber, Steve Guinter, Mark A. Hamilton, Stanley R. Harlid, Sophia Heisler, Lawrence E. Hidaka, Akihisa Hopper, John L. Huang, Wen-Yi Huyghe, Jeroen R. Jenkins, Mark A. Krzyzanowski, Paul M. Lemire, Mathieu Lin, Yi Luo, Xuemei Mardis, Elaine R. McPherson, John D. Miller, Jessica K. Moreno Aguado, Víctor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nikolaos G. Pasternack, Danielle Quist, Michael J. Rafikova, Adilya Reid, Emma E. G. Shinbrot, Eve Shirts, Brian H. Stein, Lincoln D. Teney, Cherie D. Timms, Lee Um, Caroline Y. Van Guelpen, Bethany Van Tassel, Megan Wang, Xiaolong Wheeler, David A. Yung, Christina K. Hsu, Li Ogino, Shuji Gsur, Andrea Newcomb, Polly A. Gallinger, Steven Hoffmeister, Michael Campbell, Peter T. Thibodeau, Stephen N. Sun, Wei Hudson, Thomas J. Peters, Ulrike |
| author_role |
author |
| author2 |
Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert S. Trinh, Quang M. Qu, Conghui Banbury, Barbara L. Georgeson, Peter Grasso, Catherine S. Giannakis, Marios Adams, Jeremy B. Alwers, Elizabeth Amitay, Efrat L. Barfield, Richard T. Berndt, Sonja I. Borozan, Ivan Brenner, Hermann Brezina, Stefanie Buchanan, Daniel D. Cao, Yin Chan, Andrew T. Chang-Claude, Jenny Connolly, Charles M. Drew, David A. Farris III, Alton Brad Figueiredo, Jane C. French, Amy J. Fuchs, Charles S. Garraway, Levi A. Gruber, Steve Guinter, Mark A. Hamilton, Stanley R. Harlid, Sophia Heisler, Lawrence E. Hidaka, Akihisa Hopper, John L. Huang, Wen-Yi Huyghe, Jeroen R. Jenkins, Mark A. Krzyzanowski, Paul M. Lemire, Mathieu Lin, Yi Luo, Xuemei Mardis, Elaine R. McPherson, John D. Miller, Jessica K. Moreno Aguado, Víctor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nikolaos G. Pasternack, Danielle Quist, Michael J. Rafikova, Adilya Reid, Emma E. G. Shinbrot, Eve Shirts, Brian H. Stein, Lincoln D. Teney, Cherie D. Timms, Lee Um, Caroline Y. Van Guelpen, Bethany Van Tassel, Megan Wang, Xiaolong Wheeler, David A. Yung, Christina K. Hsu, Li Ogino, Shuji Gsur, Andrea Newcomb, Polly A. Gallinger, Steven Hoffmeister, Michael Campbell, Peter T. Thibodeau, Stephen N. Sun, Wei Hudson, Thomas J. 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 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 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 Carcinogènesi Colorectal cancer Carcinogenesis |
| topic |
Càncer colorectal Carcinogènesi Colorectal cancer Carcinogenesis |
| description |
Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2021 2021 2021 |
| 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/2445/173462 |
| url |
https://hdl.handle.net/2445/173462 |
| 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/s41467-020-17386-z Nature Communications, 2020, vol. 11 https://doi.org/10.1038/s41467-020-17386-z |
| dc.rights.none.fl_str_mv |
cc by (c) Zaidi et al., 2020 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc by (c) Zaidi et al., 2020 http://creativecommons.org/licenses/by/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
12 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Ciències Clíniques) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869405101188186112 |
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15,198674 |