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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

Hui Shen, Brooke L. Fridley, Honglin Song, Kate Lawrenson, Julie M. Cunningham, Susan J. Ramus, Mine S. Cicek, Jonathan Tyrer, Douglas Stram, Melissa C. Larson, Martin Köbel, PRACTICAL Consortium, Argyrios Ziogas, Wei Zheng, Hannah P. Yang, Anna H. Wu, Eva L. Wozniak, Yin Ling Woo, Boris Winterhoff, Elisabeth Wik, Alice S. Whittemore, Nicolas Wentzensen, Rachel Palmieri Weber, Allison F. Vitonis, Daniel Vincent, Robert A. Vierkant, Ignace Vergote, David Van Den Berg, Anne M. Van Altena, Shelley S. Tworoger, Pamela J. Thompson, Daniel C. Tessier, Kathryn L. Terry, Soo-Hwang Teo, Claire Templeman, Daniel O. Stram, Melissa C. Southey, Weiva Sieh, Nadeem Siddiqui, Yurii B. Shvetsov, Xiao-Ou Shu, Viji Shridhar, Shan Wang-Gohrke, Gianluca Severi, Ira Schwaab, Helga B. Salvesen, Iwona K. Rzepecka, Ingo B. Runnebaum, Mary Anne Rossing, Lorna Rodriguez-Rodriguez, Harvey A. Risch, Stefan P. Renner, Elizabeth M. Poole, Malcolm C. Pike, Catherine M. Phelan, Liisa M. Pelttari, Tanja Pejovic, James Paul, Irene Orlow, Siti Zawiah Omar, Sara H. Olson, Kunle Odunsi, Stefan Nickels, Heli Nevanlinna, Roberta B. Ness, Steven A. Narod, Toru Nakanishi, Kirsten B. Moysich, Alvaro N.A. Monteiro, Joanna Moes-Sosnowska, Francesmary Modugno, Usha Menon, John R. McLaughlin, Valerie McGuire, Keitaro Matsuo, Noor Azmi Mat Adenan, Leon F.A.G Massuger, Galina Lurie, Lene Lundvall, Jan Lubiński, Jolanta Lissowska, Douglas A. Levine, Arto Leminen, Alice W. Lee, Nhu D. Le, Sandrina Lambrechts, Diether Lambrechts, Jolanta Kupryjanczyk, Camilla Krakstad, Gottfried E. Konecny, Susanne Krüger Kjaer, Lambertus A. Kiemeney, Linda E. Kelemen, Gary L. Keeney, Beth Y. Karlan, Rod Karevan, Kimberly R. Kalli, Hiroaki Kajiyama, Bu-Tian Ji, Allan Jensen, Anna Jakubowska, Edwin Iversen, Satoyo Hosono, Claus K. Høgdall, Estrid Høgdall, Maureen Hoatlin, Peter Hillemanns, Florian Heitz, Rebecca Hein, Philipp Harter, Mari K. Halle, Per Hall, Jacek Gronwald, Martin Gore, Marc T. Goodman, Graham G. Giles, Aleksandra Gentry-Maharaj, Montserrat Garcia-Closas, James M. Flanagan, Peter A. Fasching, Arif B. Ekici, Robert Edwards, Diana Eccles, Douglas F. Easton, Matthias Dürst, Andreas du Bois, Thilo Dörk, Jennifer A. Doherty, Evelyn Despierre, Agnieszka Dansonka-Mieszkowska, Cezary Cybulski, Daniel W. Cramer, Linda S. Cook, Xiaoqing Chen, Bridget Charbonneau, Jenny Chang-Claude, Ian Campbell, Ralf Butzow, Clareann H. Bunker, Doerthe Brueggmann, Robert Brown, Angela Brooks-Wilson, Louise A. Brinton, Natalia Bogdanova, Matthew S. Block, Elizabeth Benjamin, Jonathan Beesley, Matthias W. Beckmann, Elisa V. Bandera, Laura Baglietto, François Bacot, Sebastian M. Armasu, Natalia Antonenkova, Hoda Anton-Culver, Katja K. Aben, Dong Liang, Xifeng Wu, Karen Lu, Michelle A.T. Hildebrandt, Australian Ovarian Cancer Study Group, Australian Cancer Study, Joellen M. Schildkraut, Thomas A. Sellers, David Huntsman, Andrew Berchuck, Georgia Chenevix-Trench, Simon A. Gayther, Paul D.P. Pharoah, Peter W. Laird, Ellen L. Goode, Celeste Leigh Pearce

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. More... »

PAGES

1628

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

4

Author Affiliations

  • University of Southern California
  • University of Kansas Medical Center
  • University of Cambridge
  • Mayo Clinic
  • University of Calgary
  • University of California, Irvine
  • National Cancer Institute
  • University College London
  • University of Malaya
  • University of Bergen
  • Stanford University
  • Duke University Hospital
  • McGill University and Génome Québec Innovation Centre
  • Universitaire Ziekenhuizen Leuven
  • Radboud University Nijmegen Medical Centre
  • Harvard University
  • University of Hawaii at Manoa
  • University of Melbourne
  • Glasgow Royal Infirmary
  • University of Ulm
  • Centrum Onkologii Instytut
  • Jena University Hospital
  • University of Washington
  • Rutgers University
  • Yale University
  • Memorial Sloan Kettering Cancer Center
  • Moffitt Cancer Center
  • Helsinki University Central Hospital
  • Oregon Health & Science University
  • Beatson West of Scotland Cancer Centre
  • Roswell Park Cancer Institute
  • German Cancer Research Center
  • The University of Texas Health Science Center at Houston
  • University of Toronto
  • Okazaki City Hospital
  • University of Pittsburgh
  • Lunenfeld-Tanenbaum Research Institute
  • Aichi Cancer Center
  • Pomeranian Medical University
  • BC Cancer Agency
  • KU Leuven
  • University of California Los Angeles
  • Danish Cancer Society
  • Cedars-Sinai Medical Center
  • Nagoya University
  • Duke University
  • University of Copenhagen
  • Hannover Medical School
  • Helios Dr. Horst Schmidt Kliniken Wiesbaden
  • University of Cologne
  • Karolinska Institute
  • Royal Marsden Hospital
  • Monash University
  • Institute of Cancer Research
  • Imperial College London
  • University of Erlangen-Nuremberg
  • Dartmouth College
  • University of New Mexico
  • QIMR Berghofer Medical Research Institute
  • Texas Southern University
  • The University of Texas MD Anderson Cancer Center
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms2629

    DOI

    http://dx.doi.org/10.1038/ncomms2629

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1013482907

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23535649


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