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

Author

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

Subjects
Science
Abstract

Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Published
2020
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2. Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival

Author

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

Subjects
0301 basic medicine, Colorectal cancer, Carcinogenesis, General Physics and Astronomy, 02 engineering and technology, Disease, medicine.disease_cause, INDEL Mutation, Cancer genomics, 2.1 Biological and endogenous factors, Carcinogènesi, Tumour-suppressor proteins, lcsh:Science, Cancer, Mutation, Multidisciplinary, High-Throughput Nucleotide Sequencing, Prognosis, 021001 nanoscience & nanotechnology, Neoplasm Proteins, Colo-Rectal Cancer, Colonic Neoplasms, Medical genetics, Colorectal Neoplasms, 0210 nano-technology, Medical Genetics, medicine.medical_specialty, Science, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, MUTYH, Càncer colorectal, Genetics, medicine, Humans, Indel, neoplasms, Gene, Medicinsk genetik, Cancer och onkologi, General Chemistry, medicine.disease, digestive system diseases, 030104 developmental biology, Cancer and Oncology, Cancer research, lcsh:Q, Tumor Suppressor Protein p53, Digestive Diseases
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., Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.

Published
2020

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