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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 principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371703/ https://www.ncbi.nlm.nih.gov/pubmed/32686686 http://dx.doi.org/10.1038/s41467-020-17386-z |
| _version_ | 1783561160920924160 |
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| author | Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert 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, 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, Victor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nickolas 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_facet | Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert 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, 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, Victor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nickolas 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_sort | Zaidi, Syed H. |
| collection | PubMed |
| 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. |
| format | Online Article Text |
| id | pubmed-7371703 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-73717032020-07-22 Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert 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, 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, Victor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nickolas 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 Nat Commun Article 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. Nature Publishing Group UK 2020-07-20 /pmc/articles/PMC7371703/ /pubmed/32686686 http://dx.doi.org/10.1038/s41467-020-17386-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Zaidi, Syed H. Harrison, Tabitha A. Phipps, Amanda I. Steinfelder, Robert 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, 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, Victor Mu, Xinmeng Jasmine Nishihara, Reiko Papadopoulos, Nickolas 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 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 |
| 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_short | 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 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371703/ https://www.ncbi.nlm.nih.gov/pubmed/32686686 http://dx.doi.org/10.1038/s41467-020-17386-z |
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