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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
Nature, Volume 578, No. 7793, Year 2020
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Description
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. © 2020, The Author(s).
Authors & Co-Authors
Abascal, Federico
United Kingdom, Hinxton
Wellcome Sanger Institute
Shapira, Ofer
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Dana-farber Cancer Institute
Tiao, Grace
United States, Cambridge
Massachusetts Institute of Technology
Kim, Jaegil
United States, Cambridge
Massachusetts Institute of Technology
Bandopadhayay, Pratiti
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Dana-farber Cancer Institute
Boroevich, Keith Anthony
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Fonseca, Nuno A.
United Kingdom, Hinxton
European Molecular Biology Laboratory
Kahles, André
United States, New York
Memorial Sloan-kettering Cancer Center
Komorowski, Jan
Sweden, Solna
Science for Life Laboratory
Poland, Warszawa
Polish Academy of Sciences
Lehmann, Kjong Van
United States, New York
Memorial Sloan-kettering Cancer Center
Saksena, Gordon
United States, Cambridge
Massachusetts Institute of Technology
Schumacher, Steven E.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Dana-farber Cancer Institute
Stewart, Chip
United States, Cambridge
Massachusetts Institute of Technology
Tubío, José Manuel C.
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Spain, Vigo
Universidade de Vigo
Hobolth, Asger
Denmark, Aarhus
Aarhus Universitet
Kellis, Manolis
United States, Cambridge
Massachusetts Institute of Technology
Lawrence, Michael S.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
Nakagawa, Hidewaki
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Rubin, Mark A.
United States, New York
Weill Cornell Medicine
Tsunoda, Tatsuhiko
Japan, Yokohama
Riken Center for Integrative Medical Sciences
Japan, Tokyo
Tokyo Medical and Dental University
Japan, Tokyo
Graduate School of Medicine
Wheeler, David A.
United States, Houston
Baylor College of Medicine
Gerstein, Mark B.
United States, New Haven
Yale University
Campbell, Peter J.
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Cambridge
University of Cambridge
Bader, Gary D.
Canada, Toronto
University of Toronto
Beroukhim, Rameen
United States, Cambridge
Massachusetts Institute of Technology
United States, Cambridge
Harvard University
United States, Boston
Dana-farber Cancer Institute
Brunak, Søren B.
Denmark, Lyngby
Technical University of Denmark
Denmark, Copenhagen
Københavns Universitet
Gambacorti Passerini, Carlo B.
Italy, Milan
Università Degli Studi Di Milano-bicocca
Getz, Gad A.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Gut, I. Glynne
Spain, Barcelona
Barcelona Institute of Science and Technology Bist
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Harmanci, Arif Ozgun
United States, New Haven
Yale University
United States, Houston
University of Texas Health Science Center at Houston
Helmy, Mohamed
Canada, Toronto
University of Toronto
Korbel, Jan O.
United Kingdom, Hinxton
European Molecular Biology Laboratory
Germany, Heidelberg
European Molecular Biology Laboratory Heidelberg
Marchal, Kathleen
Belgium, Ghent
Universiteit Gent
Martincorena, Iñigo
United Kingdom, Hinxton
Wellcome Sanger Institute
Meyerson, William U.
United States, New Haven
Yale University
Pulido-Tamayo, Sergio
Belgium, Ghent
Universiteit Gent
Shackleton, Mark J.
Australia, Melbourne
Peter Maccallum Cancer Centre
Valencia, Alfonso
Spain, Barcelona
Centro Nacional de Supercomputación
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Verbeke, Lieven P.C.
Belgium, Ghent
Universiteit Gent
Warrell, Jonathan H.
United States, New Haven
Yale University
Waszak, Sebastian M.
Germany, Heidelberg
European Molecular Biology Laboratory Heidelberg
Yu, Jun
Hong Kong, Hong Kong
Chinese University of Hong Kong
Zhao, Zhongming Ming
United States, Houston
University of Texas Health Science Center at Houston
Akdemir, Kadir Caner
United States, Houston
The University of Texas Md Anderson Cancer Center
Baez-Ortega, Adrian
United Kingdom, Cambridge
University of Cambridge
Boutros, Paul C.
Canada, Toronto
Ontario Institute for Cancer Research
Canada, Toronto
University of Toronto
United States, Los Angeles
University of California, Los Angeles
Bowtell, David D.L.
Australia, Melbourne
Peter Maccallum Cancer Centre
Brors, Benedikt
Germany, Heidelberg
German Cancer Research Center
Cortes-Ciriano, Isidro
United Kingdom, Cambridge
University of Cambridge
United States, Boston
Harvard Medical School
Estivill, Xavier
Spain, Barcelona
Barcelona Institute of Science and Technology Bist
Etemadmoghadam, Dariush
Australia, Melbourne
Peter Maccallum Cancer Centre
Frenkel-Morgenstern, Milana
Israel, Ramat Gan
Bar-ilan University
Hutter, Barbara
Germany, Heidelberg
German Cancer Research Center
Jones, David T.W.
Germany, Heidelberg
German Cancer Research Center
Lynch, Andy G.
United Kingdom, Cambridge
University of Cambridge
United Kingdom, St Andrews
School of Medicine
Macintyre, Geoff
United Kingdom, Cambridge
University of Cambridge
Meyerson, Matthew L.
United States, Cambridge
Massachusetts Institute of Technology
United States, Boston
Harvard Medical School
United States, Boston
Dana-farber Cancer Institute
Switzerland, Bern
University of Bern
Australia, Melbourne
University of Melbourne
Miyano, Satoru
Japan, Tokyo
The University of Tokyo
Ossowski, Stephan
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Barcelona
Barcelona Institute of Science and Technology Bist
Germany, Tubingen
Eberhard Karls Universität Tübingen
Park, Peter J.
United States, Boston
Harvard Medical School
United States, Cambridge
Harvard University
Yoon, Sung-soo
South Korea, Seoul
Seoul National University Hospital
Zamora, Jorge
Spain, Santiago de Compostela
Universidad de Santiago de Compostela
Spain, Vigo
Universidade de Vigo
United Kingdom, Hinxton
Wellcome Sanger Institute
Statistics
Citations: 308
Authors: 62
Affiliations: 81
Identifiers
Doi:
10.1038/s41586-020-1965-x
ISSN:
00280836
Research Areas
Cancer