ITEM METADATA RECORD
Title: Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
Authors: Shen, Hui ×
Fridley, Brooke L
Song, Honglin
Lawrenson, Kate
Cunningham, Julie M
Ramus, Susan J
Cicek, Mine S
Tyrer, Jonathan
Stram, Douglas
Larson, Melissa C
Köbel, Martin
PRACTICAL Consortium
Ziogas, Argyrios
Zheng, Wei
Yang, Hannah P
Wu, Anna H
Wozniak, Eva L
Ling Woo, Yin
Winterhoff, Boris
Wik, Elisabeth
Whittemore, Alice S
Wentzensen, Nicolas
Palmieri Weber, Rachel
Vitonis, Allison F
Vincent, Daniel
Vierkant, Robert A
Vergote, Ignace
Van Den Berg, David
Van Altena, Anne M
Tworoger, Shelley S
Thompson, Pamela J
Tessier, Daniel C
Terry, Kathryn L
Teo, Soo-Hwang
Templeman, Claire
Stram, Daniel O
Southey, Melissa C
Sieh, Weiva
Siddiqui, Nadeem
Shvetsov, Yurii B
Shu, Xiao-Ou
Shridhar, Viji
Wang-Gohrke, Shan
Severi, Gianluca
Schwaab, Ira
Salvesen, Helga B
Rzepecka, Iwona K
Runnebaum, Ingo B
Anne Rossing, Mary
Rodriguez-Rodriguez, Lorna
Risch, Harvey A
Renner, Stefan P
Poole, Elizabeth M
Pike, Malcolm C
Phelan, Catherine M
Pelttari, Liisa M
Pejovic, Tanja
Orlow, Irene
Zawiah Omar, Siti
Olson, Sara H
Odunsi, Kunle
Nickels, Stefan
Nevanlinna, Heli
Ness, Roberta B
Narod, Steven A
Nakanishi, Toru
Moysich, Kirsten B
Monteiro, Alvaro N A
Moes-Sosnowska, Joanna
Modugno, Francesmary
Menon, Usha
McLaughlin, John R
McGuire, Valerie
Matsuo, Keitaro
Mat Adenan, Noor Azmi
Massuger, Leon F A G
Lurie, Galina
Lundvall, Lene
Lubiński, Jan
Lissowska, Jolanta
Levine, Douglas A
Leminen, Arto
Lee, Alice W
Le, Nhu D
Lambrechts, Sandrina
Lambrechts, Diether
Kupryjanczyk, Jolanta
Krakstad, Camilla
Konecny, Gottfried E
Krüger Kjaer, Susanne
Kiemeney, Lambertus A
Kelemen, Linda E
Keeney, Gary L
Karlan, Beth Y
Karevan, Rod
Kalli, Kimberly R
Kajiyama, Hiroaki
Ji, Bu-Tian
Jensen, Allan
Jakubowska, Anna
Iversen, Edwin
Hosono, Satoyo
Høgdall, Claus K
Høgdall, Estrid
Hoatlin, Maureen
Hillemanns, Peter
Heitz, Florian
Hein, Rebecca
Harter, Philipp
Halle, Mari K
Hall, Per
Gronwald, Jacek
Gore, Martin
Goodman, Marc T
Giles, Graham G
Gentry-Maharaj, Aleksandra
Garcia-Closas, Montserrat
Flanagan, James M
Fasching, Peter A
Ekici, Arif B
Edwards, Robert
Eccles, Diana
Easton, Douglas F
Dürst, Matthias
du Bois, Andreas
Dörk, Thilo
Doherty, Jennifer A
Despierre, Evelyn
Dansonka-Mieszkowska, Agnieszka
Cybulski, Cezary
Cramer, Daniel W
Cook, Linda S
Chen, Xiaoqing
Charbonneau, Bridget
Chang-Claude, Jenny
Campbell, Ian
Butzow, Ralf
Bunker, Clareann H
Brueggmann, Doerthe
Brown, Robert
Brooks-Wilson, Angela
Brinton, Louise A
Bogdanova, Natalia
Block, Matthew S
Benjamin, Elizabeth
Beesley, Jonathan
Beckmann, Matthias W
Bandera, Elisa V
Baglietto, Laura
Bacot, François
Armasu, Sebastian M
Antonenkova, Natalia
Anton-Culver, Hoda
Aben, Katja K
Liang, Dong
Wu, Xifeng
Lu, Karen
Hildebrandt, Michelle A T
stralian Ovarian Cancer Study Group
stralian Cancer Study
Schildkraut, Joellen M
Sellers, Thomas A
Huntsman, David
Berchuck, Andrew
Chenevix-Trench, Georgia
Gayther, Simon A
Pharoah, Paul D P
Laird, Peter W
Goode, Ellen L
Leigh Pearce, Celeste #
Issue Date: Mar-2013
Series Title: Nature Communications vol:4 pages:1628
Article number: 10.1038/ncomms2629
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.
ISSN: 2041-1723
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
× corresponding author
# (joint) last author

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