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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus
Cancer Research, Volume 79, No. 3, Year 2019
Notification
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Description
Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. © 2018 American Association for Cancer Research.
Authors & Co-Authors
Tyrer, Jonathan P.
United Kingdom, Cambridge
University of Cambridge
Mendoza, Gustavo A.
United States, Tampa
Moffitt Cancer Center
Lawrenson, Kate
United States, Los Angeles
Cedars-sinai Medical Center
Hazelett, Dennis J.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
United States, Los Angeles
Cedars-sinai Medical Center
Lyra, Paulo C.
United States, Tampa
Moffitt Cancer Center
Coetzee, Simon G.
United States, Los Angeles
Cedars-sinai Medical Center
Shen, Howard C.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Earp, Madalene A.
United States, Rochester
Mayo Clinic
Risch, Harvey A.
United States, New Haven
Yale University
Chenevix-Trench, Georgia
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Ramus, Susan J.
Australia, Sydney
Unsw Sydney
Australia, Sydney
The Kinghorn Cancer Centre
Phelan, Catherine M.
United States, Tampa
Moffitt Cancer Center
Coetzee, Gerhard A.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
United States
Van Andel Institute
Noushmehr, Houtan
United States, Detroit
Henry Ford Health System
Sellers, Thomas
United States, Tampa
Moffitt Cancer Center
Goode, Ellen L.
United States, Rochester
Mayo Clinic
Pharoah, Paul D.P.
United Kingdom, Cambridge
University of Cambridge
Gayther, Simon A.
United States, Los Angeles
Cedars-sinai Medical Center
Monteiro, Alvaro N.A.
United States, Tampa
Moffitt Cancer Center
Fridley, Brooke L.
United States, Tampa
Moffitt Cancer Center
Aben, Katja K.H.
Netherlands, Nijmegen
Radboud Universiteit
Netherlands, Utrecht
Netherlands Comprehensive Cancer Organization
Kiemeney, Lambertus A.L.M.
Netherlands, Nijmegen
Radboud Universiteit
Anton-Culver, Hoda
United States, Irvine
University of California, Irvine
Ziogas, Argyrios
United States, Irvine
University of California, Irvine
Bruinsma, Fiona Jane
Australia, East Melbourne
Cancer Council Victoria
Milne, Roger L.
Australia, East Melbourne
Cancer Council Victoria
United Kingdom, London
University College London
Bandera, E. V.
United States, New Brunswick
Rutgers Cancer Institute of new Jersey
Giles, Graham G.
United States, New Brunswick
Rutgers Cancer Institute of new Jersey
Australia, Melbourne
University of Melbourne
Bean, Yukie T.
United States, Portland
Oregon Health & Science University
Pejović, Tanja
United States, Portland
Oregon Health & Science University
Beckmann, Matthias Wilhelm
Unknown Affiliation
Hein, Alexander
Unknown Affiliation
Björge, Line
Norway, Bergen
Haukeland Universitetssjukehus
Norway, Bergen
Universitetet I Bergen
Fasching, Peter Andreas
Norway, Bergen
Haukeland Universitetssjukehus
United States, Los Angeles
University of California, Los Angeles
Kopperud, Reidun Kristin
Norway, Bergen
Haukeland Universitetssjukehus
Norway, Bergen
Universitetet I Bergen
Bogdanova, Natalia Valerijevna
Germany, Hannover
Hannover Medical School
Dörk, Thilo
Germany, Hannover
Hannover Medical School
Hillemanns, Peter
Germany, Hannover
Hannover Medical School
Brinton, Louise Annette
United States, Rockville
National Cancer Institute Nci
Wentzensen, Nicolas A.
United States, Rockville
National Cancer Institute Nci
Brooks-Wilson, Angela R.
Canada, Vancouver
Canada‘s Michael Smith Genome Sciences Centre
Canada, Burnaby
Simon Fraser University
Bunker, Clareann H.
United States, Pittsburgh
University of Pittsburgh Graduate School of Public Health
Bützow, Ralf C.
Finland, Helsinki
Helsinki University Hospital
Nevanlinna, Heli A.
Finland, Helsinki
Helsinki University Hospital
Campbell, I. G. G.
Australia, Melbourne
Peter Maccallum Cancer Centre
Australia, Melbourne
University of Melbourne
Southey, Melissa Caroline
Australia, Melbourne
University of Melbourne
Modugno, Francesmary
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
United States, Pittsburgh
Upmc Hillman Cancer Center
Glasspool, Rosalind M.
United Kingdom, Glasgow
Beatson West of Scotland Cancer Centre
Chang-Claude, Jenny C.
Germany, Heidelberg
German Cancer Research Center
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Rudolph, Anja
Germany, Heidelberg
German Cancer Research Center
Cook, Linda S.
United States, Albuquerque
The University of new Mexico
Cramer, Daniel William
United States, Boston
Harvard Medical School
United States, Boston
Harvard T.h. Chan School of Public Health
Terry, Kathryn L.
United States, Boston
Harvard Medical School
United States, Boston
Harvard T.h. Chan School of Public Health
Cunningham, Julie M.
United States, Rochester
Mayo Clinic
Cybulski, Cezary
Poland, Szczecin
Pomeranian Medical University in Szczecin
Gronwald, Jacek
Poland, Szczecin
Pomeranian Medical University in Szczecin
Jakubowska, Anna
Poland, Szczecin
Pomeranian Medical University in Szczecin
Lubiński, Jan
Poland, Szczecin
Pomeranian Medical University in Szczecin
Dansonka-Mieszkowska, Agnieszka
Poland, Warsaw
Maria Sklodowska-curie National Research Institute of Oncology
du Bois, Andreas
Germany, Essen
Kliniken Essen-mitte
Germany, Wiesbaden
Dr. Horst Schmidt Klinik Gmbh
Dicks, Ed M.
United Kingdom, Cambridge
University of Cambridge
Song, Honglin
United Kingdom, Cambridge
University of Cambridge
Doherty, Jennifer Anne
United States, Hanover
Geisel School of Medicine at Dartmouth
United States, Seattle
Fred Hutchinson Cancer Center
Rossing, Mary Anne
United States, Seattle
Fred Hutchinson Cancer Center
Dürst, Matthias
Germany, Jena
Friedrich-schiller-universität Jena
d'Adamo, Adamo P.
United Kingdom, Cambridge
University of Cambridge
Eccles, Diana M.
United Kingdom, Southampton
Princess Anne Hospital
Edwards, Robert P.
United States, Pittsburgh
University of Pittsburgh
Ekici, Arif Bülent
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Gao, Yutang
China, Shanghai
Shanghai Cancer Institute
Gentry-Maharaj, Aleksandra
United Kingdom, London
University College London
Goodman, Marc T.
United States, Los Angeles
Cedars-sinai Medical Center
Thompson, Pamela J.
United States, Los Angeles
Cedars-sinai Medical Center
Teo, Soo Hwang
Malaysia, Subang Jaya
Cancer Reserach Initiatives Foundation, Malaysia
Malaysia, Kuala Lumpur
Universiti Malaya
Wu, Xifeng
United States, Houston
The University of Texas Md Anderson Cancer Center
Hogdall, Estrid Vilma Solyom
Denmark, Copenhagen
Kræftens Bekæmpelse
Denmark, Hellerup
Gentofte Hospital
Jensen, Allan Ostergaard
Denmark, Copenhagen
Kræftens Bekæmpelse
Kjaer, Susanne Krûger
Denmark, Copenhagen
Kræftens Bekæmpelse
Denmark, Copenhagen
Rigshospitalet
Iversen, Edwin S.
United States, Durham
Duke University
Karlan, Beth Y.
United States, Los Angeles
Cedars-sinai Medical Center
Lester, Jenny
United States, Los Angeles
Cedars-sinai Medical Center
Oršulić, Sandra
United States, Los Angeles
Cedars-sinai Medical Center
United States, Durham
Duke University Medical Center
Walsh, Christine S.
United States, Los Angeles
Cedars-sinai Medical Center
Kelley, Joseph Leo
United States, Pittsburgh
University of Pittsburgh School of Medicine
Lambrechts, Diether
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Leuven
Ku Leuven
VERGOTE, Ignace B.P.
Belgium, Leuven
Leuvens Kankerinstituut
Levine, Douglas A.
United States, New York
New York University
Liang, Dong
United States, Houston
Texas Southern University
Lissowska, Jolanta
Poland, Warsaw
Maria Sklodowska-curie National Research Institute of Oncology
Lu, Karen H.
United States, Houston
The University of Texas Md Anderson Cancer Center
Massuger, Leon F.A.G.
Netherlands, Nijmegen
Radboud University Medical Center
Matsuo, Keitaro
Japan, Nagoya
Aichi Cancer Center Hospital and Research Institute
McGuire, Valerie M.
United States, Stanford
Stanford University School of Medicine
Menon, Usha
United Kingdom, London
Mrc Clinical Trials Unit
Moysich, Kirsten Barbara
United States, Buffalo
Roswell Park Cancer Institute
Ness, Roberta B.
United States, Houston
University of Texas School of Public Health
Odunsi, Kunle O.
United States, Buffalo
Roswell Park Cancer Institute
Olson, Sara H.
United States, New York
Memorial Sloan-kettering Cancer Center
Orlow, Irene
United States, Durham
Duke University Medical Center
Pike, Malcolm C.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Wu, Anna H.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Permuth, Jennifer B.
United States, Tampa
Moffitt Cancer Center
Tworoger, Shelley S.
United States, Tampa
Moffitt Cancer Center
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard T.h. Chan School of Public Health
Poole, Elizabeth M.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard T.h. Chan School of Public Health
Rosen, Barry P.
Canada, Toronto
Princess Margaret Cancer Centre
Canada, Toronto
University of Toronto
Shu, Xiaoou
United States, Nashville
Vanderbilt University School of Medicine
Shvetsov, Yurii B.
United States, Honolulu
University of Hawaiʻi Cancer Center
Wilkens, Lynne Ross
United States, New York
Icahn School of Medicine at Mount Sinai
Sieh, Weiva
United States, New York
Icahn School of Medicine at Mount Sinai
Sucheston-Campbell, Lara E.
United States, Columbus
The Ohio State University
Wang-Gohrke, Shan
Germany, Ulm
Universität Ulm
Whittemore, Alice S.
United States, Stanford
Stanford University School of Medicine
Woo, Y. L.
Malaysia, Kuala Lumpur
Universiti Malaya
Zheng, Wei
United States, Nashville
Vanderbilt University School of Medicine
Berchuck, Andrew
United States, Durham
Duke University Medical Center
Schildkraut, Joellen M.
United States, Charlottesville
University of Virginia
Kelemen, Linda E.
United States, Charleston
Medical University of South Carolina
Freedman, Matthew Lee
United States, Boston
Dana-farber Cancer Institute
Statistics
Citations: 15
Authors: 118
Affiliations: 86
Identifiers
Doi:
10.1158/0008-5472.CAN-17-3864
ISSN:
00085472
Research Areas
Cancer
Genetics And Genomics