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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.
Rheinbay, Esther; Nielsen, Morten Muhlig; Abascal, Federico; Wala, Jeremiah A; Shapira, Ofer; Tiao, Grace; Hornshøj, Henrik; Hess, Julian M; Juul, Randi Istrup; Lin, Ziao; Feuerbach, Lars; Sabarinathan, Radhakrishnan; Madsen, Tobias; Kim, Jaegil; Mularoni, Loris; Shuai, Shimin; Lanzós, Andrés; Herrmann, Carl; Maruvka, Yosef E; Shen, Ciyue; Amin, Samirkumar B; Bandopadhayay, Pratiti; Bertl, Johanna; Boroevich, Keith A; Busanovich, John; Carlevaro-Fita, Joana; Chakravarty, Dimple; Chan, Calvin Wing Yiu; Craft, David; Dhingra, Priyanka; Diamanti, Klev; Fonseca, Nuno A; Gonzalez-Perez, Abel; Guo, Qianyun; Hamilton, Mark P; Haradhvala, Nicholas J; Hong, Chen; Isaev, Keren; Johnson, Todd A; Juul, Malene; Kahles, Andre; Kahraman, Abdullah; Kim, Youngwook; Komorowski, Jan; Kumar, Kiran; Kumar, Sushant; Lee, Donghoon; Lehmann, Kjong-Van; Li, Yilong; Liu, Eric Minwei.
Afiliação
  • Rheinbay E; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nielsen MM; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.
  • Abascal F; Harvard Medical School, Boston, MA, USA.
  • Wala JA; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Shapira O; Wellcome Trust Sanger Institute, Hinxton, UK.
  • Tiao G; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hornshøj H; Bioinformatics and Integrative Genomics, Harvard University, Cambridge, MA, USA.
  • Hess JM; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Juul RI; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lin Z; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Feuerbach L; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Sabarinathan R; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Madsen T; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Kim J; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mularoni L; Harvard University, Cambridge, MA, USA.
  • Shuai S; Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Lanzós A; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Herrmann C; Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain.
  • Maruvka YE; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Shen C; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Amin SB; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Bandopadhayay P; Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Spain.
  • Bertl J; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Boroevich KA; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Busanovich J; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Carlevaro-Fita J; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
  • Chakravarty D; Department of Medical Oncology, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Chan CWY; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Craft D; Bioquant Center, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
  • Dhingra P; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Diamanti K; Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA, USA.
  • Fonseca NA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • Gonzalez-Perez A; cBio Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Guo Q; Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hamilton MP; Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX, USA.
  • Haradhvala NJ; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Hong C; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Isaev K; Department of Molecular Medicine (MOMA), Aarhus University Hospital, Aarhus, Denmark.
  • Johnson TA; Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Juul M; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kahles A; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Kahraman A; Department for BioMedical Research, University of Bern, Bern, Switzerland.
  • Kim Y; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
  • Komorowski J; Department of Medical Oncology, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Kumar K; Department of Genitourinary Medical Oncology - Research, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Kumar S; Department of Urology, Icahn school of Medicine at Mount Sinai, New York, NY, USA.
  • Lee D; Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Lehmann KV; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
  • Li Y; Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
  • Liu EM; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Nature ; 578(7793): 102-111, 2020 02.
Article em En | MEDLINE | ID: mdl-32025015
ABSTRACT
The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Mutação / Neoplasias Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Genoma Humano / Mutação / Neoplasias Limite: Humans Idioma: En Revista: Nature Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos