Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
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Published:2020-07-20
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zaidi Syed H., Harrison Tabitha A.ORCID, Phipps Amanda I., Steinfelder Robert, Trinh Quang M.ORCID, Qu Conghui, Banbury Barbara L., Georgeson PeterORCID, Grasso Catherine S., Giannakis Marios, Adams Jeremy B., Alwers Elizabeth, Amitay Efrat L.ORCID, Barfield Richard T., Berndt Sonja I., Borozan IvanORCID, Brenner Hermann, Brezina StefanieORCID, Buchanan Daniel D.ORCID, Cao Yin, Chan Andrew T.ORCID, Chang-Claude JennyORCID, Connolly Charles M., Drew David A., Farris Alton BradORCID, Figueiredo Jane C., French Amy J., Fuchs Charles S., Garraway Levi A., Gruber Steve, Guinter Mark A., Hamilton Stanley R., Harlid SophiaORCID, Heisler Lawrence E., Hidaka Akihisa, Hopper John L., Huang Wen-YiORCID, Huyghe Jeroen R.ORCID, Jenkins Mark A.ORCID, Krzyzanowski Paul M., Lemire Mathieu, Lin Yi, Luo Xuemei, Mardis Elaine R.ORCID, McPherson John D.ORCID, Miller Jessica K., Moreno VictorORCID, Mu Xinmeng Jasmine, Nishihara Reiko, Papadopoulos Nickolas, Pasternack Danielle, Quist Michael J., Rafikova Adilya, Reid Emma E. G., Shinbrot Eve, Shirts Brian H.ORCID, Stein Lincoln D., Teney Cherie D., Timms Lee, Um Caroline Y.ORCID, Van Guelpen BethanyORCID, Van Tassel Megan, Wang Xiaolong, Wheeler David A.ORCID, Yung Christina K.ORCID, Hsu Li, Ogino Shuji, Gsur AndreaORCID, Newcomb Polly A.ORCID, Gallinger Steven, Hoffmeister Michael, Campbell Peter T., Thibodeau Stephen N., Sun Wei, Hudson Thomas J., Peters UlrikeORCID
Abstract
AbstractColorectal 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Cited by
56 articles.
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