Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

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; Ulrike Peters

doi:10.1038/s41467-020-17386-z

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

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 CaoAndrew 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, Ulrike Peters

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

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.

Original language	English (US)
Article number	3644
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-17386-z
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-020-17386-z

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Zaidi, S. H., Harrison, T. A., Phipps, A. I., Steinfelder, R., Trinh, Q. M., Qu, C., Banbury, B. L., Georgeson, P., Grasso, C. S., Giannakis, M., Adams, J. B., Alwers, E., Amitay, E. L., Barfield, R. T., Berndt, S. I., Borozan, I., Brenner, H., Brezina, S., Buchanan, D. D., ... Peters, U. (2020). Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival. Nature communications, 11(1), Article 3644. https://doi.org/10.1038/s41467-020-17386-z

Zaidi, SH, Harrison, TA, Phipps, AI, Steinfelder, R, Trinh, QM, Qu, C, Banbury, BL, Georgeson, P, Grasso, CS, Giannakis, M, Adams, JB, Alwers, E, Amitay, EL, Barfield, RT, Berndt, SI, Borozan, I, Brenner, H, Brezina, S, Buchanan, DD, Cao, Y, Chan, AT, Chang-Claude, J, Connolly, CM, Drew, DA, Farris, AB, Figueiredo, JC, French, AJ, Fuchs, CS, Garraway, LA, Gruber, S, Guinter, MA, Hamilton, SR, Harlid, S, Heisler, LE, Hidaka, A, Hopper, JL, Huang, WY, Huyghe, JR, Jenkins, MA, Krzyzanowski, PM, Lemire, M, Lin, Y, Luo, X, Mardis, ER, McPherson, JD, Miller, JK, Moreno, V, Mu, XJ, Nishihara, R, Papadopoulos, N, Pasternack, D, Quist, MJ, Rafikova, A, Reid, EEG, Shinbrot, E, Shirts, BH, Stein, LD, Teney, CD, Timms, L, Um, CY, Van Guelpen, B, Van Tassel, M, Wang, X, Wheeler, DA, Yung, CK, Hsu, L, Ogino, S, Gsur, A, Newcomb, PA, Gallinger, S, Hoffmeister, M, Campbell, PT, Thibodeau, SN, Sun, W, Hudson, TJ & Peters, U 2020, 'Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival', Nature communications, vol. 11, no. 1, 3644. https://doi.org/10.1038/s41467-020-17386-z

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title = "Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival",

abstract = "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.",

author = "Zaidi, {Syed H.} and Harrison, {Tabitha A.} and Phipps, {Amanda I.} and Robert Steinfelder and Trinh, {Quang M.} and Conghui Qu and Banbury, {Barbara L.} and Peter Georgeson and Grasso, {Catherine S.} and Marios Giannakis and Adams, {Jeremy B.} and Elizabeth Alwers and Amitay, {Efrat L.} and Barfield, {Richard T.} and Berndt, {Sonja I.} and Ivan Borozan and Hermann Brenner and Stefanie Brezina and Buchanan, {Daniel D.} and Yin Cao and Chan, {Andrew T.} and Jenny Chang-Claude and Connolly, {Charles M.} and Drew, {David A.} and Farris, {Alton Brad} and Figueiredo, {Jane C.} and French, {Amy J.} and Fuchs, {Charles S.} and Garraway, {Levi A.} and Steve Gruber and Guinter, {Mark A.} and Hamilton, {Stanley R.} and Sophia Harlid and Heisler, {Lawrence E.} and Akihisa Hidaka and Hopper, {John L.} and Huang, {Wen Yi} and Huyghe, {Jeroen R.} and Jenkins, {Mark A.} and Krzyzanowski, {Paul M.} and Mathieu Lemire and Yi Lin and Xuemei Luo and Mardis, {Elaine R.} and McPherson, {John D.} and Miller, {Jessica K.} and Victor Moreno and Mu, {Xinmeng Jasmine} and Reiko Nishihara and Nickolas Papadopoulos and Danielle Pasternack and Quist, {Michael J.} and Adilya Rafikova and Reid, {Emma E.G.} and Eve Shinbrot and Shirts, {Brian H.} and Stein, {Lincoln D.} and Teney, {Cherie D.} and Lee Timms and Um, {Caroline Y.} and {Van Guelpen}, Bethany and {Van Tassel}, Megan and Xiaolong Wang and Wheeler, {David A.} and Yung, {Christina K.} and Li Hsu and Shuji Ogino and Andrea Gsur and Newcomb, {Polly A.} and Steven Gallinger and Michael Hoffmeister and Campbell, {Peter T.} and Thibodeau, {Stephen N.} and Wei Sun and Hudson, {Thomas J.} and Ulrike Peters",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

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day = "1",

doi = "10.1038/s41467-020-17386-z",

language = "English (US)",

volume = "11",

journal = "Nature communications",

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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.

AU - Peters, Ulrike

PY - 2020/12/1

Y1 - 2020/12/1

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.

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U2 - 10.1038/s41467-020-17386-z

DO - 10.1038/s41467-020-17386-z

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C2 - 32686686

AN - SCOPUS:85088272501

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3644

ER -

Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Abstract

ASJC Scopus subject areas

UN SDGs

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