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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...

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Hauptverfasser: Zaidi, Syed H. (VerfasserIn) , Harrison, Tabitha A. (VerfasserIn) , Phipps, Amanda I. (VerfasserIn) , Steinfelder, Robert (VerfasserIn) , Trinh, Quang M. (VerfasserIn) , Qu, Conghui (VerfasserIn) , Banbury, Barbara L. (VerfasserIn) , Georgeson, Peter (VerfasserIn) , Grasso, Catherine S. (VerfasserIn) , Giannakis, Marios (VerfasserIn) , Adams, Jeremy B. (VerfasserIn) , Alwers, Elizabeth (VerfasserIn) , Amitay, Efrat L. (VerfasserIn) , Barfield, Richard T. (VerfasserIn) , Berndt, Sonja I. (VerfasserIn) , Borozan, Ivan (VerfasserIn) , Brenner, Hermann (VerfasserIn) , Brezina, Stefanie (VerfasserIn) , Buchanan, Daniel D. (VerfasserIn) , Cao, Yin (VerfasserIn) , Chan, Andrew T. (VerfasserIn) , Chang-Claude, Jenny (VerfasserIn) , Connolly, Charles M. (VerfasserIn) , Drew, David A. (VerfasserIn) , Farris, Alton Brad (VerfasserIn) , Figueiredo, Jane C. (VerfasserIn) , French, Amy J. (VerfasserIn) , Fuchs, Charles S. (VerfasserIn) , Garraway, Levi A. (VerfasserIn) , Gruber, Steve (VerfasserIn) , Guinter, Mark A. (VerfasserIn) , Hoffmeister, Michael (VerfasserIn) , Campbell, Peter T. (VerfasserIn) , Thibodeau, Stephen N. (VerfasserIn) , Sun, Wei (VerfasserIn) , Hudson, Thomas J. (VerfasserIn) , Peters, Ulrike (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 July 2020
In: Nature Communications
Year: 2020, Jahrgang: 11, Pages: 3644
ISSN:2041-1723
DOI:10.1038/s41467-020-17386-z
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-17386-z
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-17386-z
Volltext
Verfasserangaben:Syed H. Zaidi, Tabitha A. Harrison, Amanda I. Phipps, Robert Steinfelder, Quang M. Trinh, Conghui Qu, Barbara L. Banbury, Peter Georgeson, Catherine S. Grasso, Marios Giannakis, Jeremy B. Adams, Elizabeth Alwers, Efrat L. Amitay, Richard T. Barfield, Sonja I. Berndt, Ivan Borozan, Hermann Brenner, Stefanie Brezina, Daniel D. Buchanan, Yin Cao, Andrew T. Chan, Jenny Chang-Claude, Charles M. Connolly, David A. Drew, Alton Brad Farris, Jane C. Figueiredo, Amy J. French, Charles S. Fuchs, Levi A. Garraway, Steve Gruber, Mark A. Guinter, Stanley R. Hamilton, Sophia Harlid, Lawrence E. Heisler, Akihisa Hidaka, John L. Hopper, Wen-Yi Huang, Jeroen R. Huyghe, Mark A. Jenkins, Paul M. Krzyzanowski, Mathieu Lemire, Yi Lin, Xuemei Luo, Elaine R. Mardis, John D. McPherson, Jessica K. Miller, Victor Moreno, Xinmeng Jasmine Mu, Reiko Nishihara, Nickolas Papadopoulos, Danielle Pasternack, Michael J. Quist, Adilya Rafikova, Emma E.G. Reid, Eve Shinbrot, Brian H. Shirts, Lincoln D. Stein, Cherie D. Teney, Lee Timms, Caroline Y. Um, Bethany Van Guelpen, Megan Van Tassel, Xiaolong Wang, David A. Wheeler, Christina K. Yung, Li Hsu, Shuji Ogino, Andrea Gsur, Polly A. Newcomb, Steven Gallinger, Michael Hoffmeister, Peter T. Campbell, Stephen N. Thibodeau, Wei Sun, Thomas J. Hudson, and Ulrike Peters
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 12.11.2020
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-17386-z

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