Journal Article

DKFZ-2019-00554

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.

Buckley, M. A. ; Woods, N. T. ; Tyrer, J. P. ; Mendoza-Fandiño, G. ; Lawrenson, K. ; Hazelett, D. J. ; Najafabadi, H. S. ; Gjyshi, A. ; Carvalho, R. S. ; Lyra, P. C. ; Coetzee, S. G. ; Shen, H. C. ; Yang, A. W. ; Earp, M. A. ; Yoder, S. J. ; Risch, H. ; Chenevix-Trench, G. ; Ramus, S. J. ; Phelan, C. M. ; Coetzee, G. A. ; Noushmehr, H. ; Hughes, T. R. ; Sellers, T. A. ; Goode, E. L. ; Pharoah, P. D. ; Gayther, S. A. ; Monteiro, A. N. A. ; Consortium, O. C. A. (Collaboration Author) ; Rudolph, A.DKFZ* ; Chang-Claude, J.DKFZ*

2019
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/0008-5472.CAN-17-3864

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. SIGNIFICANCE: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene.See related commentary by Choi and Brown, p. 439.

---

Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2019

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

---