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

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; Lene Lundvall; Susanne Krüger Kjaer; Allan Jensen; Claus K Høgdall; Estrid Høgdall; PRACTICAL Consortium

doi:10.1038/ncomms2629

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

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 WhittemoreNicolas 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, Lene Lundvall, Susanne Krüger Kjaer, Allan Jensen, Claus K Høgdall, Estrid Høgdall, PRACTICAL Consortium

Patologi

139 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Communications
Vol/bind	4
Sider (fra-til)	1628
ISSN	2041-1722
DOI	https://doi.org/10.1038/ncomms2629
Status	Udgivet - 2013

Adgang til dokumentet

10.1038/ncomms2629

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848248/pdf/nihms483288.pdf

Citationsformater

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

Shen, H, Fridley, BL, Song, H, Lawrenson, K, Cunningham, JM, Ramus, SJ, Cicek, MS, Tyrer, J, Stram, D, Larson, MC, Köbel, M, Ziogas, A, Zheng, W, Yang, HP, Wu, AH, Wozniak, EL, Woo, YL, Winterhoff, B, Wik, E, Whittemore, AS, Wentzensen, N, Weber, RP, Vitonis, AF, Vincent, D, Vierkant, RA, Vergote, I, Van Den Berg, D, Van Altena, AM, Tworoger, SS, Thompson, PJ, Tessier, DC, 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, Lundvall, L, Kjaer, SK, Jensen, A, Høgdall, CK , Høgdall, E & PRACTICAL Consortium 2013, 'Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer', Nature Communications, bind 4, s. 1628. https://doi.org/10.1038/ncomms2629

@article{383265dc73a447b3b52dc4f8f0cd200e,

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.",

keywords = "DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Hepatocyte Nuclear Factor 1-beta, Humans, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Promoter Regions, Genetic",

author = "Hui Shen and Fridley, {Brooke L} and Honglin Song and Kate Lawrenson and Cunningham, {Julie M} and Ramus, {Susan J} and Cicek, {Mine S} and Jonathan Tyrer and Douglas Stram and Larson, {Melissa C} and Martin K{\"o}bel 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 Elisabeth Wik and Whittemore, {Alice S} and Nicolas Wentzensen and Weber, {Rachel Palmieri} 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 Tessier, {Daniel C} 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 Lene Lundvall and Kjaer, {Susanne Kr{\"u}ger} and Allan Jensen and H{\o}gdall, {Claus K} and Estrid H{\o}gdall and {PRACTICAL Consortium}",

year = "2013",

doi = "10.1038/ncomms2629",

language = "English",

volume = "4",

pages = "1628",

journal = "Nature Communications",

issn = "2041-1722",

publisher = "Nature Publishing Group",

}

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 - Woo, Yin Ling

AU - Winterhoff, Boris

AU - Wik, Elisabeth

AU - Whittemore, Alice S

AU - Wentzensen, Nicolas

AU - Weber, Rachel Palmieri

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 - Lundvall, Lene

AU - Kjaer, Susanne Krüger

AU - Jensen, Allan

AU - Høgdall, Claus K

AU - Høgdall, Estrid

AU - PRACTICAL Consortium

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.

KW - DNA Methylation

KW - Epigenesis, Genetic

KW - Female

KW - Gene Expression Profiling

KW - Genetic Predisposition to Disease

KW - Hepatocyte Nuclear Factor 1-beta

KW - Humans

KW - Ovarian Neoplasms

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

U2 - 10.1038/ncomms2629

DO - 10.1038/ncomms2629

M3 - Journal article

C2 - 23535649

SN - 2041-1722

VL - 4

SP - 1628

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater