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Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.

Publication ,  Journal Article
Shen, H; Fridley, BL; Song, H; Lawrenson, K; Cunningham, JM; Ramus, SJ; Cicek, MS; Tyrer, J; Stram, D; Larson, MC; Köbel, M; Ziogas, A; Wu, X ...
Published in: Nat Commun
2013

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1628

Location

England

Related Subject Headings

  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Humans
  • Hepatocyte Nuclear Factor 1-beta
  • Genetic Predisposition to Disease
  • Gene Expression Profiling
  • Female
  • Epigenesis, Genetic
  • DNA Methylation
 

Citation

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Chicago
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Shen, H., Fridley, B. L., Song, H., Lawrenson, K., Cunningham, J. M., Ramus, S. J., … Pearce, C. L. (2013). Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Commun, 4, 1628. https://doi.org/10.1038/ncomms2629
Shen, Hui, Brooke L. Fridley, Honglin Song, Kate Lawrenson, Julie M. Cunningham, Susan J. Ramus, Mine S. Cicek, et al. “Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.Nat Commun 4 (2013): 1628. https://doi.org/10.1038/ncomms2629.
Shen H, Fridley BL, Song H, Lawrenson K, Cunningham JM, Ramus SJ, et al. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Commun. 2013;4:1628.
Shen, Hui, et al. “Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.Nat Commun, vol. 4, 2013, p. 1628. Pubmed, doi:10.1038/ncomms2629.
Shen H, Fridley BL, Song H, Lawrenson K, Cunningham JM, Ramus SJ, Cicek MS, Tyrer J, Stram D, Larson MC, Köbel M, PRACTICAL Consortium, Ziogas A, Zheng W, Yang HP, Wu AH, Wozniak EL, Woo YL, Winterhoff B, Wik E, Whittemore AS, Wentzensen N, Weber RP, Vitonis AF, Vincent D, Vierkant RA, Vergote I, Van Den Berg D, Van Altena AM, Tworoger SS, Thompson PJ, Tessier DC, Terry KL, Teo S-H, Templeman C, Stram DO, Southey MC, Sieh W, Siddiqui N, Shvetsov YB, Shu X-O, Shridhar V, Wang-Gohrke S, Severi G, Schwaab I, Salvesen HB, Rzepecka IK, Runnebaum IB, Rossing MA, Rodriguez-Rodriguez L, Risch HA, Renner SP, Poole EM, Pike MC, Phelan CM, Pelttari LM, Pejovic T, Paul J, Orlow I, Omar SZ, Olson SH, Odunsi K, Nickels S, Nevanlinna H, Ness RB, Narod SA, Nakanishi T, Moysich KB, Monteiro ANA, Moes-Sosnowska J, Modugno F, Menon U, McLaughlin JR, McGuire V, Matsuo K, Adenan NAM, Massuger LFAG, Lurie G, Lundvall L, Lubiński J, Lissowska J, Levine DA, Leminen A, Lee AW, Le ND, Lambrechts S, Lambrechts D, Kupryjanczyk J, Krakstad C, Konecny GE, Kjaer SK, Kiemeney LA, Kelemen LE, Keeney GL, Karlan BY, Karevan R, Kalli KR, Kajiyama H, Ji B-T, Jensen A, Jakubowska A, Iversen E, Hosono S, Høgdall CK, Høgdall E, Hoatlin M, Hillemanns P, Heitz F, Hein R, Harter P, Halle MK, Hall P, Gronwald J, Gore M, Goodman MT, Giles GG, Gentry-Maharaj A, Garcia-Closas M, Flanagan JM, Fasching PA, Ekici AB, Edwards R, Eccles D, Easton DF, Dürst M, du Bois A, Dörk T, Doherty JA, Despierre E, Dansonka-Mieszkowska A, Cybulski C, Cramer DW, Cook LS, Chen X, Charbonneau B, Chang-Claude J, Campbell I, Butzow R, Bunker CH, Brueggmann D, Brown R, Brooks-Wilson A, Brinton LA, Bogdanova N, Block MS, Benjamin E, Beesley J, Beckmann MW, Bandera EV, Baglietto L, Bacot F, Armasu SM, Antonenkova N, Anton-Culver H, Aben KK, Liang D, Wu X, Lu K, Hildebrandt MAT, Australian Ovarian Cancer Study Group, Australian Cancer Study, Schildkraut JM, Sellers TA, Huntsman D, Berchuck A, Chenevix-Trench G, Gayther SA, Pharoah PDP, Laird PW, Goode EL, Pearce CL. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nat Commun. 2013;4:1628.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

2013

Volume

4

Start / End Page

1628

Location

England

Related Subject Headings

  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Ovarian Neoplasms
  • Humans
  • Hepatocyte Nuclear Factor 1-beta
  • Genetic Predisposition to Disease
  • Gene Expression Profiling
  • Female
  • Epigenesis, Genetic
  • DNA Methylation