Résumé
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.
langue originale | Anglais |
---|---|
Numéro d'article | 1628 |
journal | Nature Communications |
Volume | 4 |
Les DOIs | |
état | Publié - 11 avr. 2013 |
Modification externe | Oui |
Contient cette citation
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
Dans: Nature Communications, Vol 4, 1628, 11.04.2013.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
TY - JOUR
T1 - Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
AU - Shen, Hui
AU - Fridley, Brooke L.
AU - Song, Honglin
AU - Lawrenson, Kate
AU - Cunningham, Julie M.
AU - Ramus, Susan J.
AU - Cicek, Mine S.
AU - Tyrer, Jonathan
AU - Stram, Douglas
AU - Larson, Melissa C.
AU - Köbel, Martin
AU - Ziogas, Argyrios
AU - Zheng, Wei
AU - Yang, Hannah P.
AU - Wu, Anna H.
AU - Wozniak, Eva L.
AU - Ling Woo, Yin
AU - Winterhoff, Boris
AU - Wik, Elisabeth
AU - Whittemore, Alice S.
AU - Wentzensen, Nicolas
AU - Palmieri Weber, Rachel
AU - Vitonis, Allison F.
AU - Vincent, Daniel
AU - Vierkant, Robert A.
AU - Vergote, Ignace
AU - Van Den Berg, David
AU - Van Altena, Anne M.
AU - Tworoger, Shelley S.
AU - Thompson, Pamela J.
AU - Tessier, Daniel C.
AU - Terry, Kathryn L.
AU - Teo, Soo Hwang
AU - Templeman, Claire
AU - Stram, Daniel O.
AU - Southey, Melissa C.
AU - Sieh, Weiva
AU - Siddiqui, Nadeem
AU - Shvetsov, Yurii B.
AU - Shu, Xiao Ou
AU - Shridhar, Viji
AU - Wang-Gohrke, Shan
AU - Severi, Gianluca
AU - Schwaab, Ira
AU - Salvesen, Helga B.
AU - Rzepecka, Iwona K.
AU - Runnebaum, Ingo B.
AU - Anne Rossing, Mary
AU - Rodriguez-Rodriguez, Lorna
AU - Risch, Harvey A.
AU - Renner, Stefan P.
AU - Poole, Elizabeth M.
AU - Pike, Malcolm C.
AU - Phelan, Catherine M.
AU - Pelttari, Liisa M.
AU - Pejovic, Tanja
AU - Paul, James
AU - Orlow, Irene
AU - Zawiah Omar, Siti
AU - Olson, Sara H.
AU - Odunsi, Kunle
AU - Nickels, Stefan
AU - Nevanlinna, Heli
AU - Ness, Roberta B.
AU - Narod, Steven A.
AU - Nakanishi, Toru
AU - Moysich, Kirsten B.
AU - Monteiro, Alvaro N.A.
AU - Moes-Sosnowska, Joanna
AU - Modugno, Francesmary
AU - Menon, Usha
AU - McLaughlin, John R.
AU - McGuire, Valerie
AU - Matsuo, Keitaro
AU - Mat Adenan, Noor Azmi
AU - Massuger, Leon F.A.G.
AU - Lurie, Galina
AU - Lundvall, Lene
AU - Lubiński, Jan
AU - Lissowska, Jolanta
AU - Levine, Douglas A.
AU - Leminen, Arto
AU - Lee, Alice W.
AU - Le, Nhu D.
AU - Lambrechts, Sandrina
AU - Lambrechts, Diether
AU - Kupryjanczyk, Jolanta
AU - Krakstad, Camilla
AU - Konecny, Gottfried E.
AU - Krüger Kjaer, Susanne
AU - Kiemeney, Lambertus A.
AU - Kelemen, Linda E.
AU - Keeney, Gary L.
AU - Karlan, Beth Y.
AU - Karevan, Rod
AU - Kalli, Kimberly R.
AU - Kajiyama, Hiroaki
AU - Ji, Bu Tian
AU - Jensen, Allan
AU - Jakubowska, Anna
AU - Iversen, Edwin
AU - Hosono, Satoyo
AU - Høgdall, Claus K.
AU - Høgdall, Estrid
AU - Hoatlin, Maureen
AU - Hillemanns, Peter
AU - Heitz, Florian
AU - Hein, Rebecca
AU - Harter, Philipp
AU - Halle, Mari K.
AU - Hall, Per
AU - Gronwald, Jacek
AU - Gore, Martin
AU - Goodman, Marc T.
AU - Giles, Graham G.
AU - Gentry-Maharaj, Aleksandra
AU - Garcia-Closas, Montserrat
AU - Flanagan, James M.
AU - Fasching, Peter A.
AU - Ekici, Arif B.
AU - Edwards, Robert
AU - Eccles, Diana
AU - Easton, Douglas F.
AU - Dürst, Matthias
AU - Du Bois, Andreas
AU - Dörk, Thilo
AU - Doherty, Jennifer A.
AU - Despierre, Evelyn
AU - Dansonka-Mieszkowska, Agnieszka
AU - Cybulski, Cezary
AU - Cramer, Daniel W.
AU - Cook, Linda S.
AU - Chen, Xiaoqing
AU - Charbonneau, Bridget
AU - Chang-Claude, Jenny
AU - Campbell, Ian
AU - Butzow, Ralf
AU - Bunker, Clareann H.
AU - Brueggmann, Doerthe
AU - Brown, Robert
AU - Brooks-Wilson, Angela
AU - Brinton, Louise A.
AU - Bogdanova, Natalia
AU - Block, Matthew S.
AU - Benjamin, Elizabeth
AU - Beesley, Jonathan
AU - Beckmann, Matthias W.
AU - Bandera, Elisa V.
AU - Baglietto, Laura
AU - Bacot, François
AU - Armasu, Sebastian M.
AU - Antonenkova, Natalia
AU - Anton-Culver, Hoda
AU - Aben, Katja K.
AU - Liang, Dong
AU - Wu, Xifeng
AU - Lu, Karen
AU - Hildebrandt, Michelle A.T.
AU - Schildkraut, Joellen M.
AU - Sellers, Thomas A.
AU - Huntsman, David
AU - Berchuck, Andrew
AU - Chenevix-Trench, Georgia
AU - Gayther, Simon A.
AU - Pharoah, Paul D.P.
AU - Laird, Peter W.
AU - Goode, Ellen L.
AU - Leigh Pearce, Celeste
PY - 2013/4/11
Y1 - 2013/4/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875904387&partnerID=8YFLogxK
U2 - 10.1038/ncomms2629
DO - 10.1038/ncomms2629
M3 - Article
C2 - 23535649
AN - SCOPUS:84875904387
SN - 2041-1723
VL - 4
JO - Nature Communications
JF - Nature Communications
M1 - 1628
ER -