Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Buckley MA, Woods NT, Tyrer JP, Mendoza-Fandino G, Lawrenson K, Hazelett DJ, Najafabadi HS, Gjyshi A, Carvalho RS, Lyra PC, Coetzee SG, Shen HC, Yang AW, Earp MA, Yoder SJ, Risch H, Chenevix-Trench G, Ramus SJ, Phelan CM, Coetzee GA, Noushmehr H, Hughes TR, Sellers TA, Goode EL, Pharoah PD, Gayther SA, Monteiro ANA, Chen YA, Fridley BL, Aben KKH, Kiemeney LA, Anton-Culver H, Ziogas A, Bruinsma F, Milne RL, Bandera EV, Giles GG, Bean YT, Pejovic T, Beckmann M, Hein A, Bjorge L, Fasching PA, Thomsen LCV, Kopperud RK, Bischof K, Bogdanova N, Doek T, Hillemanns P, Brinton LA, Wentzensen N, Yang H, Brooks-Wilson A, Bunker CH, Butzow R, Nevanlinna H, Pelttari LM, Campbell IG, Southey MC, Modugno F, Carty K, Glasspool R, Mcneish I, Paul J, Siddiqui N, Chang-Claude J, Rudolph A, Chang-Claude J, Cook LS, Cramer DW, Terry KL, Cunningham JM, Cybulski C, Gronwald J, Jakubowska A, Lubinski J, Dansonka-Mieszkowska A, Kupryjanczyk J, Rzepecka IK, Du Bois A, Harter P, Dicks E, Song H, Doherty JA, Rossing MA, Duerst M, Easton DF, Eccles DM, Edwards RP, Ekici AB, Fasching P, Gao YT, Milne RL, Gentry-Maharaj A, Giles GG, Goodman MT, Thompson PJ, Hasmad HN, Teo SH, Hildebrandt MAT, Wu X, Hogdall E, Jensen A, Kjaer SK, Hogdall E, Iversen ES, Karlan BY, Lester J, Orsulic S, Walsh CS, Kelley JL, Lambrechts D, Lambrechts S, Vergote I, Lee AW, Levine DA, Liang D, Lissowska J, Lu K, Lundvall L, Kjaer SK, Massuger LFAG, Van Altena AM, Matsuo K, Mcguire V, Mclaughlin JR, Menon U, Moysich KB, Ness RB, Odunsi K, Olson SH, Orlow I, Pike MC, Pearce CL, Wu AH, Permuth JB, Tsai YY, Tworoger SS, Poole EM, Rosen B, Shu XO, Shvetsov YB, Wilkens LR, Sieh W, Spiewankiewicz B, Sucheston-Campbell L, Thomsen L, Wang-Gohrke S, Whittemore AS, Woo YL, Zheng W, Berchuck A, Chenevix-Trench G, Schildkraut JM, Kelemen LE, Freedman ML
Zeitschrift: Cancer Research
Jahr der Veröffentlichung: 2019
Band: 79
Heftnummer: 3
ISSN: 0008-5472


Abstract

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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


Einrichtungen weiterer Autorinnen und Autoren

Aichi Cancer Center Research Institute
Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
California State University (CSUF)
Cancer Council Victoria
Cedars-Sinai Medical Center
Dana–Farber Cancer Institute
Danish Cancer Society Research Center
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Duke University
Friedrich-Schiller-Universität Jena
Glasgow Royal Infirmary (GRI)
Haukeland University Hospital / Haukeland universitetssykehus
Helsingin yliopisto / University of Helsinki
Henry Ford Health System (HFHS)
H. Lee Moffitt Cancer Center & Research Institute
Icahn School of Medicine at Mount Sinai
Institute for Oncology Ljubljana (OIL)
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
Kliniken Essen-Mitte
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
Medical University of South Carolina (MUSC)
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
New York University (NYU)
Ohio State University
Oregon Health and Science University (OSHU)
Peter MacCallum Cancer Centre
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
Princess Anne Hospital
Public Health Ontario
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Radboud University Nijmegen
Ramsay Sime Darby Health Care (RSDHC)
Roswell Park Cancer Institute
Rutgers Cancer Institute of New Jersey
Shanghai Cancer Institute / 上海市肿瘤研究所
Stanford University
Texas Southern University (TSU)
The University of Melbourne
Universität Ulm
University College London (UCL)
University of California Irvine
University of Cambridge
University of Copenhagen
University of Hawaii (U.H.)
University of Malaya (UM) / Universiti Malaya
University of New Mexico
University of New South Wales (UNSW)
University of Pittsburgh
University of Southern California (USC)
University of Texas MD Anderson Cancer Center
University of Toronto
University of Virginia (UVA)
University of Washington
Vanderbilt University


Zitierweisen

APA:
Buckley, M.A., Woods, N.T., Tyrer, J.P., Mendoza-Fandino, G., Lawrenson, K., Hazelett, D.J.,... Freedman, M.L. (2019). Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus. Cancer Research, 79(3). https://dx.doi.org/10.1158/0008-5472.CAN-17-3864

MLA:
Buckley, Melissa A., et al. "Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus." Cancer Research 79.3 (2019).

BibTeX: 

Zuletzt aktualisiert 2019-21-07 um 07:57