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

Autor: Zaidi SH; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Harrison TA; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Phipps AI; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Steinfelder R; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Trinh QM; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Banbury BL; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Georgeson P; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3010, Australia., Grasso CS; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Surgery, Cedar Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA., Giannakis M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA., Adams JB; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Alwers E; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Amitay EL; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Barfield RT; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Borozan I; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Brezina S; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschekagasse 8a, 1090, Vienna, Austria., Buchanan DD; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3010, Australia.; Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia., Cao Y; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Boston, MA, 02114, USA.; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.; Division of Public Health Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, USA., Chan AT; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Boston, MA, 02114, USA.; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Avenue, Boston, MA, 02115, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Avenue, Boston, MA, 02115, USA., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.; Cancer Epidemiology Group, University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), 20246, Hamburg, Germany., Connolly CM; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Drew DA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Boston, MA, 02114, USA.; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA., Farris AB 3rd; Pathology and Laboratory Medicine, Emory University School of Medicine, 1364 Clifton Rd. NE, Atlanta, GA, 30322, USA., Figueiredo JC; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., French AJ; Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Fuchs CS; Yale Cancer Center, 333 Cedar St, New Haven, CT, 06510, USA.; Department of Medicine, Yale School of Medicine, New Haven, CT, USA.; Smilow Cancer Hospital, New Haven, CT, USA., Garraway LA; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA., Gruber S; Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA, 90089, USA., Guinter MA; Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St NW, Atlanta, GA, 30303, USA., Hamilton SR; City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA., Harlid S; Department of Radiation Sciences, Oncology Unit, Umeå University, SE-901 87, Umeå, Sweden., Heisler LE; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Hidaka A; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Hopper JL; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3010, Australia., Huang WY; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Huyghe JR; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Jenkins MA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, 3010, Australia., Krzyzanowski PM; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Lemire M; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Lin Y; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Luo X; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Mardis ER; Institute for Genomic Medicine, Nationwide Children's Hospital and The Ohio State University College of Medicine, 575 Children's Crossroad, Columbus, OH, 43215, USA., McPherson JD; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada.; Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, 2700 Stockton Blvd, Sacramento, CA, 95817, USA., Miller JK; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Moreno V; Oncology Data Analytics Program, Catalan Institute of Oncology and ONCOBELL Program, IDIBELL, Avinguda de la Granvia de l'Hospitalet 199-203, 08908, L'Hospitalet de Llobregat, Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain.; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, 08907, Barcelona, Spain., Mu XJ; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA., Nishihara R; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA., Papadopoulos N; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Institution, 1650 Orleans Street, Baltimore, MD, 21231, USA., Pasternack D; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Quist MJ; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Rafikova A; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Reid EEG; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Shinbrot E; Human Genome Sequencing Centre, Baylor College of Medicine, One Baylor Plaza, Alkek N1419, Houston, TX, 77030, USA., Shirts BH; Department of Laboratory Medicine, University of Washington, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA, 98195, USA., Stein LD; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Teney CD; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Timms L; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Um CY; Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St NW, Atlanta, GA, 30303, USA., Van Guelpen B; Department of Radiation Sciences, Oncology Unit, Umeå University, SE-901 87, Umeå, Sweden.; Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87, Umeå, Sweden., Van Tassel M; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Wang X; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Wheeler DA; Human Genome Sequencing Centre, Baylor College of Medicine, One Baylor Plaza, Alkek N1419, Houston, TX, 77030, USA., Yung CK; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Hsu L; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Biostatistics, University of Washington, Seattle, WA, USA., Ogino S; Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA, 02142, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, 677 Huntington Avenue, Boston, MA, 02115, USA.; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA., Gsur A; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschekagasse 8a, 1090, Vienna, Austria., Newcomb PA; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA.; Department of Epidemiology, University of Washington, Seattle, WA, USA., Gallinger S; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada.; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.; Department of Surgery, University Health Network Toronto General Hospital, Toronto, ON, Canada., Hoffmeister M; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Campbell PT; Behavioral and Epidemiology Research Group, American Cancer Society, 250 Williams St NW, Atlanta, GA, 30303, USA., Thibodeau SN; Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA., Sun W; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA., Hudson TJ; Ontario Institute for Cancer Research, 661 University Avenue, Toronto, ON, M5G 0A3, Canada., Peters U; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, 1100 Fairview Ave N, Seattle, WA, 98109, USA. upeters@fredhutch.org.; Department of Epidemiology, University of Washington, Seattle, WA, USA. upeters@fredhutch.org.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Jul 20; Vol. 11 (1), pp. 3644. Date of Electronic Publication: 2020 Jul 20.
DOI: 10.1038/s41467-020-17386-z
Abstrakt: 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.
Databáze: MEDLINE