Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Glubb DM, Johnatty SE, Quinn MCJ, O'Mara TA, Tyrer JP, Gao B, Fasching P, Beckmann M, Lambrechts D, Vergote I, Edwards DRV, Beeghly-Fadiel A, Benitez J, Garcia MJ, Goodman MT, Thompson PJ, Doerk T, Duerst M, Modungo F, Moysich K, Heitz F, Du Bois A, Pfisterer J, Hillemanns P, Karlan BY, Lester J, Goode EL, Cunningham JM, Winham SJ, Larson MC, Mccauley BM, Kjaer SK, Jensen A, Schildkraut JM, Berchuck A, Cramer DW, Terry KL, Salvesen HB, Bjorge L, Webb PM, Grant P, Pejovic T, Moffitt M, Hogdall CK, Hogdall E, Paul J, Glasspool R, Bernardini M, Tone A, Huntsman D, Woo M, Defazio A, Kennedy CJ, Pharoah PDP, Macgregor S, Chenevix-Trench G
Zeitschrift: Oncotarget
Jahr der Veröffentlichung: 2017
Band: 8
Heftnummer: 39
Seitenbereich: 64670-64684
ISSN: 1949-2553


Abstract

We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates at the 1q22 and 19p12 loci, as well as other regional variants, were nominally associated with patient outcome; however, no associations reached our threshold for statistical significance (p<1×10-5). Larger patient numbers will be needed to convincingly identify any true associations at these loci.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

Beatson West of Scotland Cancer Centre (BWSCC)
Brigham and Women's Hospital (BWH)
British Columbia Cancer Agency
Cedars-Sinai Medical Center
Danish Cancer Society Research Center
Duke University
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Friedrich-Schiller-Universität Jena
Haukeland University Hospital / Haukeland universitetssykehus
Kliniken Essen-Mitte
Mayo Clinic
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mercy Hospital for Women
Oregon Health and Science University (OSHU)
Princess Margaret Cancer Centre / Princess Margaret Hospital
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Roswell Park Cancer Institute
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Copenhagen
University of Pittsburgh
University of Sydney
University of Virginia (UVA)
Vanderbilt University
Westmead Hospital


Zitierweisen

APA:
Glubb, D.M., Johnatty, S.E., Quinn, M.C.J., O'Mara, T.A., Tyrer, J.P., Gao, B.,... Chenevix-Trench, G. (2017). Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci. Oncotarget, 8(39), 64670-64684. https://dx.doi.org/10.18632/oncotarget.18501

MLA:
Glubb, Dylan M., et al. "Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci." Oncotarget 8.39 (2017): 64670-64684.

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Zuletzt aktualisiert 2019-25-04 um 14:57