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

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 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 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

Nat Commun 2013 ;4:1628

USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/ncomms2629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848248PMC
October 2013
122 Reads

Article Mentions


Provided by Crossref Event Data
web
Web: Web
March 14, 2017, 8:00 am EST
wikipedia
Wikipedia: 분자병리역학
October 20, 2018, 1:05 am EST

Publication Analysis

Top Keywords

ovarian cancer
32
epithelial ovarian
28
clear cell
16
cancer risk
12
methylation expression
8
cancer
8
cell epithelial
8
dna methylation
8
histological subtypes
8
ovarian
8
epithelial
7
hnf1b
5
10-8 epithelial
4
serous subtype
4
higher hnf1b-promoter
4
hnf1b-promoter methylation
4
methylation tumours
4
associate higher
4
subtype associate
4
alleles serous
4

References

(Supplied by CrossRef)
Article in N. Engl. J. Med.
P Lichtenstein et al.
N. Engl. J. Med. 2000
Article in Br. J. Cancer
A Auranen et al.
Br. J. Cancer 1996
Article in Future Oncol.
AC Antoniou et al.
Future Oncol. 2006
Article in Nat. Genet.
EL Goode et al.
Nat. Genet. 2010
Article in Nat. Genet.
KL Bolton et al.
Nat. Genet. 2010
Article in Nat. Genet.
H Song et al.
Nat. Genet. 2009
Article in J. Intern. Med.
KL Bolton et al.
J. Intern. Med. 2012
Article in Am. J. Pathol.
A Tsuchiya et al.
Am. J. Pathol. 2003
Article in Nat. Genet.
Y Horikawa et al.
Nat. Genet. 1997
Article in Nat. Genet.
J Gudmundsson et al.
Nat. Genet. 2007

Similar Publications