American Association for Cancer Research
00085472can173864-sup-194003_3_supp_4928074_pcp4jb.xlsx (17.3 kB)

Supplementary Table 1 from Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus

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posted on 2023-03-31, 03:07 authored by Melissa A. Buckley, Nicholas T. Woods, Jonathan P. Tyrer, Gustavo Mendoza-Fandiño, Kate Lawrenson, Dennis J. Hazelett, Hamed S. Najafabadi, Anxhela Gjyshi, Renato S. Carvalho, Paulo C. Lyra, Simon G. Coetzee, Howard C. Shen, Ally W. Yang, Madalene A. Earp, Sean J. Yoder, Harvey Risch, Georgia Chenevix-Trench, Susan J. Ramus, Catherine M. Phelan, Gerhard A. Coetzee, Houtan Noushmehr, Timothy R. Hughes, Thomas A. Sellers, Ellen L. Goode, Paul D. Pharoah, Simon A. Gayther, Alvaro N.A. Monteiro

Primers used in this study.



Ovarian Cancer Research Foundation


American Cancer Society

California Cancer Research

Canadian Institutes for Health Research

US National Cancer Institute

US Army Medical Research and Material Command



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. 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