publication . Article . Other literature type . 2017

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

Stuart MacGregor; Tracy A. O'Mara; Bo Gao; Bo Gao; Line Bjørge; Line Bjørge; Jacobus Pfisterer; Digna R. Velez Edwards; Diether Lambrechts; Kathryn L. Terry; ...
Open Access English
  • Published: 12 Sep 2017
  • Publisher: eScholarship, University of California
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 eff...
Subjects
Medical Subject Headings: health care economics and organizations
free text keywords: AGO Study Group, /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428, Journal Article, Priority Research Paper, ovarian cancer outcome, genetic association, gene regulation, meta-analysis, TCF Transcription Factors, Disease Progression, Consortium, ENHANCERS, Promoter Regions, Genetic, MEF2D, OVEREXPRESSION, POLYMORPHISMS, transition, Gene Expression, Oncology and Carcinogenesis, Oncology, Ovarian cancer, medicine.disease, medicine, Locus (genetics), Haplotype, Genetics, Biology, Gene, Promoter, Germline
Funded by
NIH| The Mitochondrial Genome and Ovarian Cancer Risk
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA149429-05
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Inflammation and Ovarian Cancer
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA095023-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NHMRC| Australasian Biospecimen Network - Oncology
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 628903
  • Funding stream: NHMRC Enabling Grants
,
NHMRC| Towards cancer control: Population and molecular strategies
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 199600
  • Funding stream: Programs
,
NIH| COLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA058598-05
  • Funding stream: NATIONAL CANCER INSTITUTE
31 references, page 1 of 3

Dinkelspiel, HE, Champer, M, Hou, J, Tergas, A, Burke, WM, Huang, Y, Neugut, AI, Ananth, CV, Hershman, DL, Wright, JD. Long-term mortality among women with epithelial ovarian cancer. Gynecologic Oncology. 2015; 138: 421-428 [OpenAIRE] [PubMed]

Sopik, V, Iqbal, J, Rosen, B, Narod, SA. Why have ovarian cancer mortality rates declined? Part II. Case-fatality. Gynecologic Oncology. 2015; 138: 750-756 [PubMed]

Johnatty, SE, Tyrer, JP, Kar, S, Beesley, J, Lu, Y, Gao, B, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium. Clin Cancer Res. 2015; 21: 5264-5276 [OpenAIRE] [PubMed]

Mifsud, B, Tavares-Cadete, F, Young, AN, Sugar, R, Schoenfelder, S, Ferreira, L, Wingett, SW, Andrews, S, Grey, W, Ewels, PA, Herman, B, Happe, S, Higgs, A. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat Genet. 2015; 47: 598-606 [OpenAIRE] [PubMed]

Li, G, Ruan, X, Auerbach, RK, Sandhu, KS, Zheng, M, Wang, P, Poh, HM, Goh, Y, Lim, J, Zhang, J, Sim, HS, Peh, SQ, Mulawadi, FH. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell. 2012; 148: 84-98 [OpenAIRE] [PubMed]

Ardlie, KG, Deluca, DS, Segrè, AV, Sullivan, TJ, Young, TR, Gelfand, ET, Trowbridge, CA, Maller, JB, Tukiainen, T, Lek, M, Ward, LD, Kheradpour, P, Iriarte, B. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans. Science. 2015; 348: 648-660 [OpenAIRE] [PubMed]

Hou, C, Dale, R, Dean, A. Cell type specificity of chromatin organization mediated by CTCF and cohesin. Proc Natl Acad Sci U S A. 2010; 107: 3651-3656 [OpenAIRE] [PubMed]

Heinz, S, Romanoski, CE, Benner, C, Glass, CK. The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol. 2015; 16: 144-154 [OpenAIRE] [PubMed]

Hnisz, D, Abraham, BJ, Lee, TI, Lau, A, Saint-André, V, Sigova, AA, Hoke, HA, Young, RA. Super-enhancers in the control of cell identity and disease. Cell. 2013; 155: 934-947 [OpenAIRE] [PubMed]

Ørom, UA, Shiekhattar, R. Long non-coding RNAs and enhancers. Curr Opin Genet Dev. 2011; 21: 194-198 [OpenAIRE] [PubMed]

Li, S, Weidenfeld, J, Morrisey, EE. Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions. Mol Cell Biol. 2004; 24: 809-822 [OpenAIRE] [PubMed]

Choi, EJ, Seo, EJ, Kim, DK, Lee, SI, Kwon, YW, Jang, IH, Kim, KH, Suh, DS, Kim, JH. FOXP1 functions as an oncogene in promoting cancer stem cell-like characteristics in ovarian cancer cells. Oncotarget. 2016; 7: 3506-3519 [OpenAIRE] [PubMed] [DOI]

Gyorffy, B, Lanczky, A, Szallasi, Z. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012; 19: 197-208 [OpenAIRE] [PubMed]

Amos, CI, Dennis, J, Wang, Z, Byun, J, Schumacher, FR, Gayther, SA, Casey, G, Hunter, DJ, Sellers, TA, Gruber, SB, Dunning, AM, Michailidou, K, Fachal, L. The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers. Cancer Epidemiol Biomarkers Prev. 2017; 26: 126-135 [OpenAIRE] [PubMed]

Breitbart, RE, Liang, CS, Smoot, LB, Laheru, DA, Mahdavi, V, Nadal-Ginard, B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993; 118: 1095-1106 [PubMed]

31 references, page 1 of 3
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 eff...
Subjects
Medical Subject Headings: health care economics and organizations
free text keywords: AGO Study Group, /dk/atira/pure/researchoutput/pubmedpublicationtype/D016428, Journal Article, Priority Research Paper, ovarian cancer outcome, genetic association, gene regulation, meta-analysis, TCF Transcription Factors, Disease Progression, Consortium, ENHANCERS, Promoter Regions, Genetic, MEF2D, OVEREXPRESSION, POLYMORPHISMS, transition, Gene Expression, Oncology and Carcinogenesis, Oncology, Ovarian cancer, medicine.disease, medicine, Locus (genetics), Haplotype, Genetics, Biology, Gene, Promoter, Germline
Funded by
NIH| The Mitochondrial Genome and Ovarian Cancer Risk
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA149429-05
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NIH| Inflammation and Ovarian Cancer
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA095023-03
  • Funding stream: NATIONAL CANCER INSTITUTE
,
NHMRC| Australasian Biospecimen Network - Oncology
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 628903
  • Funding stream: NHMRC Enabling Grants
,
NHMRC| Towards cancer control: Population and molecular strategies
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 199600
  • Funding stream: Programs
,
NIH| COLLABORATIVE STUDY OF OVARIAN CANCER IN TWO RISK GROUPS
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01CA058598-05
  • Funding stream: NATIONAL CANCER INSTITUTE
31 references, page 1 of 3

Dinkelspiel, HE, Champer, M, Hou, J, Tergas, A, Burke, WM, Huang, Y, Neugut, AI, Ananth, CV, Hershman, DL, Wright, JD. Long-term mortality among women with epithelial ovarian cancer. Gynecologic Oncology. 2015; 138: 421-428 [OpenAIRE] [PubMed]

Sopik, V, Iqbal, J, Rosen, B, Narod, SA. Why have ovarian cancer mortality rates declined? Part II. Case-fatality. Gynecologic Oncology. 2015; 138: 750-756 [PubMed]

Johnatty, SE, Tyrer, JP, Kar, S, Beesley, J, Lu, Y, Gao, B, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I. Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes: Findings from the Ovarian Cancer Association Consortium. Clin Cancer Res. 2015; 21: 5264-5276 [OpenAIRE] [PubMed]

Mifsud, B, Tavares-Cadete, F, Young, AN, Sugar, R, Schoenfelder, S, Ferreira, L, Wingett, SW, Andrews, S, Grey, W, Ewels, PA, Herman, B, Happe, S, Higgs, A. Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C. Nat Genet. 2015; 47: 598-606 [OpenAIRE] [PubMed]

Li, G, Ruan, X, Auerbach, RK, Sandhu, KS, Zheng, M, Wang, P, Poh, HM, Goh, Y, Lim, J, Zhang, J, Sim, HS, Peh, SQ, Mulawadi, FH. Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell. 2012; 148: 84-98 [OpenAIRE] [PubMed]

Ardlie, KG, Deluca, DS, Segrè, AV, Sullivan, TJ, Young, TR, Gelfand, ET, Trowbridge, CA, Maller, JB, Tukiainen, T, Lek, M, Ward, LD, Kheradpour, P, Iriarte, B. The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans. Science. 2015; 348: 648-660 [OpenAIRE] [PubMed]

Hou, C, Dale, R, Dean, A. Cell type specificity of chromatin organization mediated by CTCF and cohesin. Proc Natl Acad Sci U S A. 2010; 107: 3651-3656 [OpenAIRE] [PubMed]

Heinz, S, Romanoski, CE, Benner, C, Glass, CK. The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol. 2015; 16: 144-154 [OpenAIRE] [PubMed]

Hnisz, D, Abraham, BJ, Lee, TI, Lau, A, Saint-André, V, Sigova, AA, Hoke, HA, Young, RA. Super-enhancers in the control of cell identity and disease. Cell. 2013; 155: 934-947 [OpenAIRE] [PubMed]

Ørom, UA, Shiekhattar, R. Long non-coding RNAs and enhancers. Curr Opin Genet Dev. 2011; 21: 194-198 [OpenAIRE] [PubMed]

Li, S, Weidenfeld, J, Morrisey, EE. Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions. Mol Cell Biol. 2004; 24: 809-822 [OpenAIRE] [PubMed]

Choi, EJ, Seo, EJ, Kim, DK, Lee, SI, Kwon, YW, Jang, IH, Kim, KH, Suh, DS, Kim, JH. FOXP1 functions as an oncogene in promoting cancer stem cell-like characteristics in ovarian cancer cells. Oncotarget. 2016; 7: 3506-3519 [OpenAIRE] [PubMed] [DOI]

Gyorffy, B, Lanczky, A, Szallasi, Z. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012; 19: 197-208 [OpenAIRE] [PubMed]

Amos, CI, Dennis, J, Wang, Z, Byun, J, Schumacher, FR, Gayther, SA, Casey, G, Hunter, DJ, Sellers, TA, Gruber, SB, Dunning, AM, Michailidou, K, Fachal, L. The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers. Cancer Epidemiol Biomarkers Prev. 2017; 26: 126-135 [OpenAIRE] [PubMed]

Breitbart, RE, Liang, CS, Smoot, LB, Laheru, DA, Mahdavi, V, Nadal-Ginard, B. A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the myogenic lineage. Development. 1993; 118: 1095-1106 [PubMed]

31 references, page 1 of 3
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