Your browser doesn't support javascript.
loading
Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus.
Buckley, Melissa A; Woods, Nicholas T; Tyrer, Jonathan P; Mendoza-Fandiño, Gustavo; Lawrenson, Kate; Hazelett, Dennis J; Najafabadi, Hamed S; Gjyshi, Anxhela; Carvalho, Renato S; Lyra, Paulo C; Coetzee, Simon G; Shen, Howard C; Yang, Ally W; Earp, Madalene A; Yoder, Sean J; Risch, Harvey; Chenevix-Trench, Georgia; Ramus, Susan J; Phelan, Catherine M; Coetzee, Gerhard A; Noushmehr, Houtan; Hughes, Timothy R; Sellers, Thomas A; Goode, Ellen L; Pharoah, Paul D; Gayther, Simon A; Monteiro, Alvaro N A.
Afiliação
  • Buckley MA; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Woods NT; University of South Florida Cancer Biology PhD Program, Tampa, Florida.
  • Tyrer JP; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Mendoza-Fandiño G; Department of Oncological Sciences, Morsani College of Medicine, University of South Florida, Tampa, Florida.
  • Lawrenson K; The Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Hazelett DJ; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Najafabadi HS; Women's Cancer Program at the Samuel Oschin Comprehensive, Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
  • Gjyshi A; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
  • Carvalho RS; Department of Urology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
  • Lyra PC; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
  • Coetzee SG; Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  • Shen HC; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Yang AW; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Earp MA; University of South Florida Cancer Biology PhD Program, Tampa, Florida.
  • Yoder SJ; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Risch H; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Chenevix-Trench G; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.
  • Ramus SJ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
  • Phelan CM; Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
  • Coetzee GA; Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.
  • Noushmehr H; Molecular Genomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Hughes TR; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
  • Sellers TA; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Goode EL; School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
  • Pharoah PD; The Kinghorn Cancer Center, Garvan Institute of Medical Research, Darlinghurst, Australia.
  • Gayther SA; Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
  • Monteiro ANA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California.
Cancer Res ; 79(3): 467-481, 2019 02 01.
Article em En | MEDLINE | ID: mdl-30487138
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.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cromossomos Humanos Par 9 / Carcinoma Epitelial do Ovário Limite: Female / Humans Idioma: En Revista: Cancer Res Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Cromossomos Humanos Par 9 / Carcinoma Epitelial do Ovário Limite: Female / Humans Idioma: En Revista: Cancer Res Ano de publicação: 2019 Tipo de documento: Article