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Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci.
Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J; O'Mara, Tracy A; Tyrer, Jonathan P; Gao, Bo; Fasching, Peter A; Beckmann, Matthias W; Lambrechts, Diether; Vergote, Ignace; Velez Edwards, Digna R; Beeghly-Fadiel, Alicia; Benitez, Javier; Garcia, Maria J; Goodman, Marc T; Thompson, Pamela J; Dörk, Thilo; Dürst, Matthias; Modungo, Francesmary; Moysich, Kirsten; Heitz, Florian; du Bois, Andreas; Pfisterer, Jacobus; Hillemanns, Peter; Karlan, Beth Y; Lester, Jenny; Goode, Ellen L; Cunningham, Julie M; Winham, Stacey J; Larson, Melissa C; McCauley, Bryan M; Kjær, Susanne Krüger; Jensen, Allan; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Salvesen, Helga B; Bjorge, Line; Webb, Penny M; Grant, Peter; Pejovic, Tanja; Moffitt, Melissa; Hogdall, Claus K; Hogdall, Estrid; Paul, James; Glasspool, Rosalind; Bernardini, Marcus; Tone, Alicia; Huntsman, David.
Afiliación
  • Glubb DM; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Johnatty SE; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Quinn MCJ; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • O'Mara TA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Tyrer JP; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
  • Gao B; Crown Princess Mary Cancer Care Centre, Westmead Hospital, Sydney, NSW, Australia.
  • Fasching PA; Center for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia.
  • Beckmann MW; University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology and Oncology, Los Angeles, CA, USA.
  • Lambrechts D; University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Vergote I; University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
  • Velez Edwards DR; Vesalius Research Center, VIB, Leuven, Belgium.
  • Beeghly-Fadiel A; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.
  • Benitez J; Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Garcia MJ; Vanderbilt Epidemiology Center, Vanderbilt Genetics Institute, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Goodman MT; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Thompson PJ; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Dörk T; Human Genetics Group, Spanish National Cancer Centre (CNIO), and Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
  • Dürst M; Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Modungo F; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Moysich K; Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Heitz F; Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • du Bois A; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Pfisterer J; Department of Gynaecology, University of Jena, Jena, Germany.
  • Hillemanns P; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Karlan BY; Ovarian Cancer Center of Excellence, University of Pittsburgh, Pittsburgh, PA, USA.
  • Lester J; Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA.
  • Goode EL; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
  • Cunningham JM; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
  • Winham SJ; Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
  • Larson MC; Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
  • McCauley BM; Zentrum für Gynäkologische Onkologie, Kiel, Germany.
  • Kjær SK; Department of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
  • Schildkraut JM; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Berchuck A; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Cramer DW; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Terry KL; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Salvesen HB; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Bjorge L; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Webb PM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
  • Grant P; Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Pejovic T; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Moffitt M; Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark.
  • Hogdall CK; Department of Public Health Sciences, The University of Virginia, Charlottesville, VA, USA.
  • Hogdall E; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
  • Paul J; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Glasspool R; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Bernardini M; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
  • Tone A; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
  • Huntsman D; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
Oncotarget ; 8(39): 64670-64684, 2017 Sep 12.
Article en En | MEDLINE | ID: mdl-29029385
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Oncotarget Año: 2017 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos