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

Shen, H., Fridley, B. L., Song, H., Lawrenson, K., Cunningham, J. M., Ramus, S. J., Cicek, M. S., Tyrer, J., Stram, D., Larson, M. C., Kobel, M., Ziogas, A., Zheng, W., Yang, H. P., Wu, A. H., Wozniak, E. L., Ling Woo, Y., Winterhoff, B., Wik, E., Whittemore, A. S., Wentzensen, N., Palmieri Weber, R., Vitonis, A. F., Vincent, D., Vierkant, R. A., Vergote, I., Van Den Berg, D., Van Altena, A. M., Tworoger, S. S., Thompson, P. J., Tessier, D. C., Terry, K. L., Teo, S. -H., Templeman, C., Stram, D. O., Southey, M. C., Sieh, W., Siddiqui, N., Shvetsov, Y. B., Shu, X. -O., Shridhar, V., Wang-Gohrke, S., Severi, G., Schwaab, I., Salvesen, H. B., Rzepecka, I. K., Runnebaum, I. B., Anne Rossing, M., Rodriguez-Rodriguez, L., Risch, H. A., Renner, S. P., Poole, E. M., Pike, M. C., Phelan, C. M., Pelttari, L. M., Pejovic, T., Paul, J., Orlow, I., Zawiah Omar, S., Olson, S. H., Odunsi, K., Nickels, S., Nevanlinna, H., Ness, R. B., Narod, S. A., Nakanishi, T., Moysich, K. B., Monteiro, A. N. A., Moes-Sosnowska, J., Modugno, F., Menon, U., McLaughlin, J. R., McGuire, V., Matsuo, K., Mat Adenan, N. A., Massuger, L. F. A. G., Lurie, G., Lundvall, L., Lubinski, J., Lissowska, J., Levine, D. A., Leminen, A., Lee, A. W., Le, N. D., Lambrechts, S., Lambrechts, D., Kupryjanczyk, J., Krakstad, C., Konecny, G. E., Kruger Kjaer, S., Kiemeney, L. A., Kelemen, L. E., Keeney, G. L., Karlan, B. Y., Karevan, R., Kalli, K. R., Kajiyama, H., Ji, B. -T., Jensen, A., Jakubowska, A., Iversen, E., Hosono, S., Hogdall, C. K., Hogdall, E., Hoatlin, M., Hillemanns, P., Heitz, F., Hein, R., Harter, P., Halle, M. K., Hall, P., Gronwald, J., Gore, M., Goodman, M. T., Giles, G. G., Gentry-Maharaj, A., Garcia-Closas, M., Flanagan, J. M., Fasching, P. A., Ekici, A. B., Edwards, R., Eccles, D., Easton, D. F., Durst, M., Du Bois, A., Dork, T., Doherty, J. A., Despierre, E., Dansonka-Mieszkowska, A., Cybulski, C., Cramer, D. W., Cook, L.S., Chen, X., Charbonneau, B., Chang-Claude, J., Campbell, I., Butzow, R., Bunker, C. H., Brueggmann, D., Brown, R., Brooks-Wilson, A., Brinton, L. A., Bogdanova, N., Block, M. S., Benjamin, E., Beesley, J., Beckmann, M. W., Bandera, E. V., Baglietto, L., Bacot, F., Armasu, S. M., Antonenkova, N., Anton-Culver, H., Aben, K. K., Liang, D., Wu, X., Lu, K., Hildebrandt, M. A. T., Schildkraut, J. M., Sellers, T. A., Huntsman, D., Berchuck, A., Chenevix-Trench, G., Gayther, S. A., Pharoah, P. D. P., Laird, P. W., Goode, E. L. and Leigh Pearce, C. (2013) Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nature Communications, 4 Article number: 1628: 1-10. doi:10.1038/ncomms2629

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Author Shen, H.
Fridley, B. L.
Song, H.
Lawrenson, K.
Cunningham, J. M.
Ramus, S. J.
Cicek, M. S.
Tyrer, J.
Stram, D.
Larson, M. C.
Kobel, M.
Ziogas, A.
Zheng, W.
Yang, H. P.
Wu, A. H.
Wozniak, E. L.
Ling Woo, Y.
Winterhoff, B.
Wik, E.
Whittemore, A. S.
Wentzensen, N.
Palmieri Weber, R.
Vitonis, A. F.
Vincent, D.
Vierkant, R. A.
Vergote, I.
Van Den Berg, D.
Van Altena, A. M.
Tworoger, S. S.
Thompson, P. J.
Tessier, D. C.
Terry, K. L.
Teo, S. -H.
Templeman, C.
Stram, D. O.
Southey, M. C.
Sieh, W.
Siddiqui, N.
Shvetsov, Y. B.
Shu, X. -O.
Shridhar, V.
Wang-Gohrke, S.
Severi, G.
Schwaab, I.
Salvesen, H. B.
Rzepecka, I. K.
Runnebaum, I. B.
Anne Rossing, M.
Rodriguez-Rodriguez, L.
Risch, H. A.
Renner, S. P.
Poole, E. M.
Pike, M. C.
Phelan, C. M.
Pelttari, L. M.
Pejovic, T.
Paul, J.
Orlow, I.
Zawiah Omar, S.
Olson, S. H.
Odunsi, K.
Nickels, S.
Nevanlinna, H.
Ness, R. B.
Narod, S. A.
Nakanishi, T.
Moysich, K. B.
Monteiro, A. N. A.
Moes-Sosnowska, J.
Modugno, F.
Menon, U.
McLaughlin, J. R.
McGuire, V.
Matsuo, K.
Mat Adenan, N. A.
Massuger, L. F. A. G.
Lurie, G.
Lundvall, L.
Lubinski, J.
Lissowska, J.
Levine, D. A.
Leminen, A.
Lee, A. W.
Le, N. D.
Lambrechts, S.
Lambrechts, D.
Kupryjanczyk, J.
Krakstad, C.
Konecny, G. E.
Kruger Kjaer, S.
Kiemeney, L. A.
Kelemen, L. E.
Keeney, G. L.
Karlan, B. Y.
Karevan, R.
Kalli, K. R.
Kajiyama, H.
Ji, B. -T.
Jensen, A.
Jakubowska, A.
Iversen, E.
Hosono, S.
Hogdall, C. K.
Hogdall, E.
Hoatlin, M.
Hillemanns, P.
Heitz, F.
Hein, R.
Harter, P.
Halle, M. K.
Hall, P.
Gronwald, J.
Gore, M.
Goodman, M. T.
Giles, G. G.
Gentry-Maharaj, A.
Garcia-Closas, M.
Flanagan, J. M.
Fasching, P. A.
Ekici, A. B.
Edwards, R.
Eccles, D.
Easton, D. F.
Durst, M.
Du Bois, A.
Dork, T.
Doherty, J. A.
Despierre, E.
Dansonka-Mieszkowska, A.
Cybulski, C.
Cramer, D. W.
Cook, L.S.
Chen, X.
Charbonneau, B.
Chang-Claude, J.
Campbell, I.
Butzow, R.
Bunker, C. H.
Brueggmann, D.
Brown, R.
Brooks-Wilson, A.
Brinton, L. A.
Bogdanova, N.
Block, M. S.
Benjamin, E.
Beesley, J.
Beckmann, M. W.
Bandera, E. V.
Baglietto, L.
Bacot, F.
Armasu, S. M.
Antonenkova, N.
Anton-Culver, H.
Aben, K. K.
Liang, D.
Wu, X.
Lu, K.
Hildebrandt, M. A. T.
Schildkraut, J. M.
Sellers, T. A.
Huntsman, D.
Berchuck, A.
Chenevix-Trench, G.
Gayther, S. A.
Pharoah, P. D. P.
Laird, P. W.
Goode, E. L.
Leigh Pearce, C.
Title Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2013
Sub-type Article (original research)
DOI 10.1038/ncomms2629
Open Access Status DOI
Volume 4
Issue Article number: 1628
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2014
Language eng
Abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 55 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 23 Feb 2014, 09:57:50 EST by Matthew Lamb on behalf of School of Medicine