Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

SG Coetzee; HC Shen; DJ Hazelett; K Lawrenson; K Kuchenbaecker; J Tyrer; SK Rhie; K Levanon; A Karst; R Drapkin; SJ Ramus; FJ Couch; K Offit; G Chenevix-Trench; ANA Monteiro; A Antoniou; M Freedman; GA Coetzee; PDP Pharoah; H Noushmehr; SA Gayther; H Anton-Culver; N Antonenkova; H Baker; EV Bandera; Y Bean; MW Beckmann; A Berchuck; M Bisogna; L Bjorge; N Bogdanova; LA Brinton; A Brooks-Wilson; F Bruinsma; R Butzow; IG Campbell; K Carty; J Chang-Claude; A Chen; Z Chen; LS Cook; DW Cramer; JM Cunningham; C Cybulski; A Dansonka-Mieszkowska; J Dennis; E Dicks; JA Doherty; T Dörk; AD Bois; M Dürst; D Eccles; DF Easton; RP Edwards; U Eilber; AB Ekici; PA Fasching; BL Fridley; YT Gao; A Gentry-Maharaj; GG Giles; R Glasspool; EL Goode; MT Goodman; J Grownwald; P Harrington; P Harter; HN Hasmad; A Hein; F Heitz; MAT Hildebrandt; P Hillemanns; E Hogdall; C Hogdall; S Hosono; ES Iversen; A Jakubowska; P James; A Jensen; BT Ji; BY Karlan; SK Kjaer; LE Kelemen; M Kellar; JL Kelley; LA Kiemeney; C Krakstad; J Kupryjanczyk; D Lambrechts; S Lambrechts; ND Le; S Lele; A Leminen; J Lester; DA Levine; D Liang; J Lissowska; K Lu; J Lubinski; L Lundvall

Journal article

Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci

SG Coetzee, HC Shen, DJ Hazelett, K Lawrenson, K Kuchenbaecker, J Tyrer, SK Rhie, K Levanon, A Karst, R Drapkin, SJ Ramus, FJ Couch, K Offit, G Chenevix-Trench, ANA Monteiro, A Antoniou, M Freedman, GA Coetzee, PDP Pharoah, H Noushmehr Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2015

DOI: 10.1093/hmg/ddv101

Abstract

Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most singlenucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types w..

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University of Melbourne Researchers

Fiona Bruinsma Author

Graham Giles Author

Melissa Southey Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

This study was supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112), a Program Project Development Grant from the Ovarian Cancer Research Fund (to S.A.G. and A.M.) and a pilot award from the Clinical and Translational Science Institute at USC to K.L. and S.A.G. K.L. is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). The in vitro aspects of this project were performed within the Norris Cancer Centre at USC, which is supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.