Buckley, MA;
Woods, NT;
Tyrer, JP;
Mendoza-Fandiño, G;
Lawrenson, K;
Hazelett, DJ;
Najafabadi, HS;
... Freedman, ML; + view all
(2019)
Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.
Cancer Research
, 79
(3)
pp. 467-481.
10.1158/0008-5472.CAN-17-3864.
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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.
| Type: | Article |
|---|---|
| Title: | Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1158/0008-5472.CAN-17-3864 |
| Publisher version: | https://doi.org/10.1158/0008-5472.CAN-17-3864 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.` |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10068235 |
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