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

Hui Shen; Brooke Fridley; Honglin Song; Kate Lawrenson; Julie Cunningham; Susan J Ramus; Mine S Cicek; Jonathan Tyrer; Douglas Stram; Melissa Larson; Martin Kobel; Argyrios Ziogas; Wei Zheng; Hannah P Yang; Anna H Wu; Eva L Wozniak; Yin Ling Woo; Boris Winterhoff; Elizabeth Wik; Alice S Whittemore; Nicolas Wentzensen; Rachel 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 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 Monteiro; Joanna Moes-Sosnowska; Francesmary Modugno; Usha N Menon; John R McLaughlin; Valerie McGuire; Keitaro Matsuo; Noor A M Adenan; Leon F A G Massuger; Galina Lurie; Lene Lundvall; Jan Lubinski; Jolanta Lissowska; Douglas Levine; Arto Leminen; Alice W Lee; Nhu Le; Sandrina Lambrechts; Diether Lambrechts; Jolanta Kupryjanczyk; Camilla Krakstad; Gottfried E Konecny; Susanne Kruger Kjaer; Lambertus Kiemeney; Linda Kelemen; Gary L Keeney; Beth Karlan; Rod Karevan; Kimberly Kalli; Hiroaki Kajiyama; Bu-tian Ji; Allan Jensen; Anna Jakubowska; Edwin Iversen; Satoyo Hosono; Claus Hogdall; Estrid Hogdall; Maureen Hoatlin; Peter Hillemanns; Florian Heitz; Rebecca Hein; Philipp Harter; Mari Halle; Per Hall; Jacek Gronwald; Martin Gore; Marc T Goodman; Graham Giles; Aleksandra Gentry-Maharaj; Montserrat Garcia-Closas; James Flanagan; Peter Fasching; Arif B Ekici; Robert Edwards; Diana M Eccles; Douglas F Easton; Matthias Duerst; Andreas Du Bois; Thilo Dork; Jennifer Doherty; Evelyn Despierre; Agnieszka Dansonka-Mieszkowska; Cezary Cybulski; Daniel Cramer; Linda Cook; Xiaoqing Chen; Bridget Charbonneau; Jenny Chang-Claude; Ian G Campbell; Ralf Butzow; Clareann H Bunker; Doerthe Brueggmann; Robert Brown; Angela Brooks-Wilson; Louise Brinton; Natalia Bogdanova; Matthew S Block; Elizabeth Benjamin; Jonathan Beesley; Matthias Beckmann; Elisa Bandera; Laura Baglietto; Francois Bacot; Sebastian 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 Pharoah; Peter W Laird; Ellen L Goode; Celeste L Pearce

doi:10.1038/ncomms2629

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

Hui Shen, Brooke Fridley, Honglin Song, Kate Lawrenson, Julie Cunningham, Susan J Ramus, Mine S Cicek, Jonathan Tyrer, Douglas Stram, Melissa Larson, Martin Kobel, Argyrios Ziogas, Wei Zheng, Hannah P Yang, Anna H Wu, Eva L Wozniak, Yin Ling Woo, Boris Winterhoff, Elizabeth Wik, Alice S WhittemoreNicolas Wentzensen, Rachel 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 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 Monteiro, Joanna Moes-Sosnowska, Francesmary Modugno, Usha N Menon, John R McLaughlin, Valerie McGuire, Keitaro Matsuo, Noor A M Adenan, Leon F A G Massuger, Galina Lurie, Lene Lundvall, Jan Lubinski, Jolanta Lissowska, Douglas Levine, Arto Leminen, Alice W Lee, Nhu Le, Sandrina Lambrechts, Diether Lambrechts, Jolanta Kupryjanczyk, Camilla Krakstad, Gottfried E Konecny, Susanne Kruger Kjaer, Lambertus Kiemeney, Linda Kelemen, Gary L Keeney, Beth Karlan, Rod Karevan, Kimberly Kalli, Hiroaki Kajiyama, Bu-tian Ji, Allan Jensen, Anna Jakubowska, Edwin Iversen, Satoyo Hosono, Claus Hogdall, Estrid Hogdall, Maureen Hoatlin, Peter Hillemanns, Florian Heitz, Rebecca Hein, Philipp Harter, Mari Halle, Per Hall, Jacek Gronwald, Martin Gore, Marc T Goodman, Graham Giles, Aleksandra Gentry-Maharaj, Montserrat Garcia-Closas, James Flanagan, Peter Fasching, Arif B Ekici, Robert Edwards, Diana M Eccles, Douglas F Easton, Matthias Duerst, Andreas Du Bois, Thilo Dork, Jennifer Doherty, Evelyn Despierre, Agnieszka Dansonka-Mieszkowska, Cezary Cybulski, Daniel Cramer, Linda Cook, Xiaoqing Chen, Bridget Charbonneau, Jenny Chang-Claude, Ian G Campbell, Ralf Butzow, Clareann H Bunker, Doerthe Brueggmann, Robert Brown, Angela Brooks-Wilson, Louise Brinton, Natalia Bogdanova, Matthew S Block, Elizabeth Benjamin, Jonathan Beesley, Matthias Beckmann, Elisa Bandera, Laura Baglietto, Francois Bacot, Sebastian 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 Pharoah, Peter W Laird, Ellen L Goode, Celeste L Pearce

Epidemiology and Preventive Medicine Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

143 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1 - 10
Number of pages	10
Journal	Nature Communications
Volume	4
Issue number	Art # 1628
DOIs	https://doi.org/10.1038/ncomms2629
Publication status	Published - 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ncomms2629

Cite this

Shen, H., Fridley, B., Song, H., Lawrenson, K., Cunningham, J., Ramus, S. J., Cicek, M. S., Tyrer, J., Stram, D., Larson, M., Kobel, M., Ziogas, A., Zheng, W., Yang, H. P., Wu, A. H., Wozniak, E. L., Woo, Y. L., Winterhoff, B., Wik, E., ... Pearce, C. L. (2013). Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nature Communications, 4(Art # 1628), 1 - 10. https://doi.org/10.1038/ncomms2629

@article{7a31021dd7894ffc8302404e1c0059f1,

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

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.",

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

year = "2013",

doi = "10.1038/ncomms2629",

language = "English",

volume = "4",

pages = "1 -- 10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "Art \# 1628",

}

Shen, H, Fridley, B, Song, H, Lawrenson, K, Cunningham, J, Ramus, SJ, Cicek, MS, Tyrer, J, Stram, D, Larson, M, Kobel, M, Ziogas, A, Zheng, W, Yang, HP, Wu, AH, Wozniak, EL, Woo, YL, Winterhoff, B, Wik, E, Whittemore, AS, Wentzensen, N, Weber, R, Vitonis, AF, Vincent, D, Vierkant, RA, Vergote, I, Van Den Berg, D, Van Altena, AM, Tworoger, SS, Thompson, PJ, Tessier, D, Terry, KL, Teo, S-H, Templeman, C, Stram, DO, Southey, MC, Sieh, W, Siddiqui, N, Shvetsov, YB, Shu, X-O, Shridhar, V, Wang-Gohrke, S, Severi, G, Schwaab, I, Salvesen, HB, Rzepecka, IK, Runnebaum, IB, Rossing, MA, Rodriguez-Rodriguez, L, Risch, HA, Renner, SP, Poole, EM, Pike, MC, Phelan, CM, Pelttari, LM, Pejovic, T, Paul, J, Orlow, I, Omar, SZ, Olson, SH, Odunsi, K, Nickels, S, Nevanlinna, H, Ness, RB, Narod, SA, Nakanishi, T, Moysich, KB, Monteiro, A, Moes-Sosnowska, J, Modugno, F, Menon, UN, McLaughlin, JR, McGuire, V, Matsuo, K, Adenan, NAM, Massuger, LFAG, Lurie, G, Lundvall, L, Lubinski, J, Lissowska, J, Levine, D, Leminen, A, Lee, AW, Le, N, Lambrechts, S, Lambrechts, D, Kupryjanczyk, J, Krakstad, C, Konecny, GE, Kjaer, SK, Kiemeney, L, Kelemen, L, Keeney, GL, Karlan, B, Karevan, R, Kalli, K, Kajiyama, H, Ji, B, Jensen, A, Jakubowska, A, Iversen, E, Hosono, S, Hogdall, C, Hogdall, E, Hoatlin, M, Hillemanns, P, Heitz, F, Hein, R, Harter, P, Halle, M, Hall, P, Gronwald, J, Gore, M, Goodman, MT, Giles, G, Gentry-Maharaj, A, Garcia-Closas, M, Flanagan, J, Fasching, P, Ekici, AB, Edwards, R, Eccles, DM, Easton, DF, Duerst, M, Du Bois, A, Dork, T, Doherty, J, Despierre, E, Dansonka-Mieszkowska, A, Cybulski, C, Cramer, D, Cook, L, Chen, X, Charbonneau, B, Chang-Claude, J, Campbell, IG, Butzow, R, Bunker, CH, Brueggmann, D, Brown, R, Brooks-Wilson, A, Brinton, L, Bogdanova, N, Block, MS, Benjamin, E, Beesley, J, Beckmann, M, Bandera, E, Baglietto, L, Bacot, F, Armasu, S, Antonenkova, N, Anton-Culver, H, Aben, KK, Liang, D, Wu, X, Lu, K, Hildebrandt, MAT, Schildkraut, JM, Sellers, TA, Huntsman, D, Berchuck, A, Chenevix-Trench, G, Gayther, SA, Pharoah, PD, Laird, PW, Goode, EL & Pearce, CL 2013, 'Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer', Nature Communications, vol. 4, no. Art # 1628, pp. 1 - 10. https://doi.org/10.1038/ncomms2629

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

AU - Song, Honglin

AU - Lawrenson, Kate

AU - Cunningham, Julie

AU - Ramus, Susan J

AU - Cicek, Mine S

AU - Tyrer, Jonathan

AU - Stram, Douglas

AU - Larson, Melissa

AU - Kobel, Martin

AU - Ziogas, Argyrios

AU - Zheng, Wei

AU - Yang, Hannah P

AU - Wu, Anna H

AU - Wozniak, Eva L

AU - Woo, Yin Ling

AU - Winterhoff, Boris

AU - Wik, Elizabeth

AU - Whittemore, Alice S

AU - Wentzensen, Nicolas

AU - 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

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 - Rossing, Mary Anne

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 - Omar, Siti Zawiah

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

AU - Moes-Sosnowska, Joanna

AU - Modugno, Francesmary

AU - Menon, Usha N

AU - McLaughlin, John R

AU - McGuire, Valerie

AU - Matsuo, Keitaro

AU - Adenan, Noor A M

AU - Massuger, Leon F A G

AU - Lurie, Galina

AU - Lundvall, Lene

AU - Lubinski, Jan

AU - Lissowska, Jolanta

AU - Levine, Douglas

AU - Leminen, Arto

AU - Lee, Alice W

AU - Le, Nhu

AU - Lambrechts, Sandrina

AU - Lambrechts, Diether

AU - Kupryjanczyk, Jolanta

AU - Krakstad, Camilla

AU - Konecny, Gottfried E

AU - Kjaer, Susanne Kruger

AU - Kiemeney, Lambertus

AU - Kelemen, Linda

AU - Keeney, Gary L

AU - Karlan, Beth

AU - Karevan, Rod

AU - Kalli, Kimberly

AU - Kajiyama, Hiroaki

AU - Ji, Bu-tian

AU - Jensen, Allan

AU - Jakubowska, Anna

AU - Iversen, Edwin

AU - Hosono, Satoyo

AU - Hogdall, Claus

AU - Hogdall, Estrid

AU - Hoatlin, Maureen

AU - Hillemanns, Peter

AU - Heitz, Florian

AU - Hein, Rebecca

AU - Harter, Philipp

AU - Halle, Mari

AU - Hall, Per

AU - Gronwald, Jacek

AU - Gore, Martin

AU - Goodman, Marc T

AU - Giles, Graham

AU - Gentry-Maharaj, Aleksandra

AU - Garcia-Closas, Montserrat

AU - Flanagan, James

AU - Fasching, Peter

AU - Ekici, Arif B

AU - Edwards, Robert

AU - Eccles, Diana M

AU - Easton, Douglas F

AU - Duerst, Matthias

AU - Du Bois, Andreas

AU - Dork, Thilo

AU - Doherty, Jennifer

AU - Despierre, Evelyn

AU - Dansonka-Mieszkowska, Agnieszka

AU - Cybulski, Cezary

AU - Cramer, Daniel

AU - Cook, Linda

AU - Chen, Xiaoqing

AU - Charbonneau, Bridget

AU - Chang-Claude, Jenny

AU - Campbell, Ian G

AU - Butzow, Ralf

AU - Bunker, Clareann H

AU - Brueggmann, Doerthe

AU - Brown, Robert

AU - Brooks-Wilson, Angela

AU - Brinton, Louise

AU - Bogdanova, Natalia

AU - Block, Matthew S

AU - Benjamin, Elizabeth

AU - Beesley, Jonathan

AU - Beckmann, Matthias

AU - Bandera, Elisa

AU - Baglietto, Laura

AU - Bacot, Francois

AU - Armasu, Sebastian

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

AU - Laird, Peter W

AU - Goode, Ellen L

AU - Pearce, Celeste L

PY - 2013

Y1 - 2013

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.nature.com/ncomms/journal/v4/n3/pdf/ncomms2629.pdf

U2 - 10.1038/ncomms2629

DO - 10.1038/ncomms2629

M3 - Article

SN - 2041-1723

VL - 4

SP - 1

EP - 10

JO - Nature Communications

JF - Nature Communications

IS - Art # 1628

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Cite this