Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
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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.
in: NAT COMMUN, Jahrgang 11, Nr. 1, 20.07.2020, S. 3644.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
AU - Zaidi, Syed H
AU - Harrison, Tabitha A
AU - Phipps, Amanda I
AU - Steinfelder, Robert
AU - Trinh, Quang M
AU - Qu, Conghui
AU - Banbury, Barbara L
AU - Georgeson, Peter
AU - Grasso, Catherine S
AU - Giannakis, Marios
AU - Adams, Jeremy B
AU - Alwers, Elizabeth
AU - Amitay, Efrat L
AU - Barfield, Richard T
AU - Berndt, Sonja I
AU - Borozan, Ivan
AU - Brenner, Hermann
AU - Brezina, Stefanie
AU - Buchanan, Daniel D
AU - Cao, Yin
AU - Chan, Andrew T
AU - Chang-Claude, Jenny
AU - Connolly, Charles M
AU - Drew, David A
AU - Farris, Alton Brad
AU - Figueiredo, Jane C
AU - French, Amy J
AU - Fuchs, Charles S
AU - Garraway, Levi A
AU - Gruber, Steve
AU - Guinter, Mark A
AU - Hamilton, Stanley R
AU - Harlid, Sophia
AU - Heisler, Lawrence E
AU - Hidaka, Akihisa
AU - Hopper, John L
AU - Huang, Wen-Yi
AU - Huyghe, Jeroen R
AU - Jenkins, Mark A
AU - Krzyzanowski, Paul M
AU - Lemire, Mathieu
AU - Lin, Yi
AU - Luo, Xuemei
AU - Mardis, Elaine R
AU - McPherson, John D
AU - Miller, Jessica K
AU - Moreno, Victor
AU - Mu, Xinmeng Jasmine
AU - Nishihara, Reiko
AU - Papadopoulos, Nickolas
AU - Pasternack, Danielle
AU - Quist, Michael J
AU - Rafikova, Adilya
AU - Reid, Emma E G
AU - Shinbrot, Eve
AU - Shirts, Brian H
AU - Stein, Lincoln D
AU - Teney, Cherie D
AU - Timms, Lee
AU - Um, Caroline Y
AU - Van Guelpen, Bethany
AU - Van Tassel, Megan
AU - Wang, Xiaolong
AU - Wheeler, David A
AU - Yung, Christina K
AU - Hsu, Li
AU - Ogino, Shuji
AU - Gsur, Andrea
AU - Newcomb, Polly A
AU - Gallinger, Steven
AU - Hoffmeister, Michael
AU - Campbell, Peter T
AU - Thibodeau, Stephen N
AU - Sun, Wei
AU - Hudson, Thomas J
PY - 2020/7/20
Y1 - 2020/7/20
N2 - 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.
AB - 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.
KW - Colonic Neoplasms/genetics
KW - Colorectal Neoplasms/genetics
KW - High-Throughput Nucleotide Sequencing
KW - Humans
KW - INDEL Mutation
KW - Mutation
KW - Neoplasm Proteins/genetics
KW - Prognosis
KW - Tumor Suppressor Protein p53/genetics
U2 - 10.1038/s41467-020-17386-z
DO - 10.1038/s41467-020-17386-z
M3 - SCORING: Journal article
C2 - 32686686
VL - 11
SP - 3644
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -