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oai:repisalud.isciii.es:20.500.12105/73312024-11-29T16:45:04Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Glubb, Dylan M author Johnatty, Sharon E author Quinn, Michael C J author O'Mara, Tracy A author Tyrer, Jonathan P author Gao, Bo author Fasching, Peter A author Beckmann, Matthias W author Lambrechts, Diether author Vergote, Ignace author Velez Edwards, Digna R author Beeghly-Fadiel, Alicia author Benitez, Javier author Garcia, Maria J author Goodman, Marc T author Thompson, Pamela J author Dörk, Thilo author Dürst, Matthias author Modungo, Francesmary author Moysich, Kirsten author Heitz, Florian author du Bois, Andreas author Pfisterer, Jacobus author Hillemanns, Peter author Karlan, Beth Y author Lester, Jenny author Goode, Ellen L author Cunningham, Julie M author Winham, Stacey J author Larson, Melissa C author McCauley, Bryan M author Kjær, Susanne Krüger author Jensen, Allan author Schildkraut, Joellen M author Berchuck, Andrew author Cramer, Daniel W author Terry, Kathryn L author Salvesen, Helga B author Bjorge, Line author Webb, Penny M author Grant, Peter author Pejovic, Tanja author Moffitt, Melissa author Hogdall, Claus K author Hogdall, Estrid author Paul, James author Glasspool, Rosalind author Bernardini, Marcus author Tone, Alicia author Huntsman, David author Woo, Michelle author Group, Aocs author deFazio, Anna author Kennedy, Catherine J author Pharoah, Paul D P author MacGregor, Stuart author Chenevix-Trench, Georgia author 2017-09-12 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. Oncotarget. 2017;8(39):64670-64684 10.18632/oncotarget.18501 1949-2553 1949-2553 Oncotarget 29029385 http://hdl.handle.net/20.500.12105/7331 Gene regulation Genetic association Meta-analysis Ovarian cancer outcome Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci