Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus Journal Article


Authors: 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. Jr; 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.; on behalf of the Ovarian Cancer Association Consortium
Contributor: Olson, S. H.
Article Title: Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus
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. © 2018 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 79
Issue: 3
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2019-02-01
Start Page: 467
End Page: 481
Language: English
DOI: 10.1158/0008-5472.Can-17-3864
PUBMED: 30487138
PROVIDER: scopus
PMCID: PMC6359979
DOI/URL:
Notes: Article -- Export Date: 1 March 2019 -- Source: Scopus
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  1. Sara H Olson
    213 Olson