The University of Southampton
University of Southampton Institutional Repository

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

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
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
biological sciences, cancer, genetics
1628-[10pp]
Shen, Hui
0ab92c75-afbc-4e65-a033-139d98b1c38f
Fridley, Brooke L.
d659bf17-d796-4e8f-9af5-2dff1c11deaf
Song, Honglin
90088f14-dc56-4280-83e3-71ad1744858d
Lawrenson, Kate
b1787caf-36bc-4378-a1f3-11545308f6f1
Cunningham, Julie M.
6181118b-0b2c-4af9-8d8e-241b76808ca8
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Cicek, Mine S.
b8d7736c-dc66-491b-85ed-898847799f1c
Tyrer, Jonathan
2c15ee61-c6e4-4c0a-9190-b0592bce73cc
Stram, Douglas
75fd6341-cd22-455c-8384-ee924bbcbae3
Larson, Melissa C.
c1819763-4dc3-4514-91bf-97c2cfbe6692
Köbel, Martin
34633857-78fe-445d-902a-4659f2f5fb9e
Ziogas, Argyrios
786f0e72-cf35-4301-805e-6128295e4a4f
Zheng, Wei
e8338ae7-b60e-46dd-bf1b-7648891c6fe4
Yang, Hannah P.
3c435365-a2eb-486d-8d4d-e638c486753f
Wu, Anna H.
a657c0a4-2887-4b9c-a018-a795197920e3
Wozniak, Eva L.
df1ab03e-1f87-4ec4-b7d4-97ff1f3ed825
Ling Woo, Yin
41638407-4044-4380-8161-81ab5825c584
Winterhoff, Boris
e91dfe8d-2f46-4480-8d5d-b49d5bea58cf
Wik, Elisabeth
1966758b-48f8-4bff-a8d9-be039f5a2b64
Whittemore, Alice S.
7d313f5d-6286-49a8-acb7-4e6bfafb117c
Wentzensen, Nicolas
43ddba47-f169-466d-b6aa-c2f5a20e9753
Palmieri Weber, Rachel
756bbe18-0f56-4cea-9873-52863bc273e0
Vitonis, Allison F.
20fb802a-cd81-49bf-8e98-44c35da4d35f
Vincent, Daniel
36e0c2d5-2536-4040-a97d-4f6ec074c731
Vierkant, Robert A.
2c236081-4238-4d9a-b160-f2b3d83a10f6
Vergote, Ignace
119d04aa-b069-43e7-8fef-3b3218c13e86
Van Den Berg, David
643617d5-b80b-464d-b64e-6b49afc263ac
Van Altena, Anne M.
70e14f69-ca1d-4e1d-b6b4-42dc1965607a
Tworoger, Shelley S.
7016b048-06b3-43dd-a660-2bf19b34c3c1
Thompson, Pamela J.
69df292d-f664-42f0-aec1-58d0cab4962a
Tessier, Daniel C.
ffa92c90-84dd-4328-9a3b-b5cc9b6bedef
Terry, Kathryn L.
e1358eae-c105-4a69-b240-c248939d8bdf
Teo, Soo-Hwang
56e60db6-a62d-4c7d-a63b-8245ea786c42
Templeman, Claire
27978818-32b4-424b-ac51-bb2acff915ec
Stram, Daniel O.
170b190f-c863-4768-9966-9cd43953ec81
Southey, Melissa C.
56062dff-748c-47e4-99f5-044cff9da594
Sieh, Weiva
9d5bdd00-daee-4ad2-a93c-cabf9010a00d
Siddiqui, Nadeem
96d263e8-0f61-46e9-86a8-a13e622dc450
Shvetsov, Yurii B.
7c68801c-4e42-4cee-9e0c-0ee1e4a1969f
Shu, Xiao-Ou
77f6b7c1-6f68-4030-8f69-f6003269d5da
Shridhar, Viji
a0a96a4c-c52f-4ecc-98b8-183ac0aa749c
Wang-Gohrke, Shan
5bce864c-5f22-44d2-b5a0-b53a3e7abe8e
Severi, Gianluca
e0a9b779-4324-434a-90ac-ecef87ed04ed
Schwaab, Ira
6b723711-4958-47a3-9338-73d587dac1e2
Salvesen, Helga B.
f6728260-5c3a-4714-b78c-fd741f9755c2
Rzepecka, Iwona K.
9cba996d-4e8e-4f1b-9117-3130aa6c445e
Runnebaum, Ingo B.
a16e9d3c-66b3-41a7-80a1-5663f75f52da
Anne Rossing, Mary
18f7ab9e-1570-4dea-a065-258b492f594c
Rodriguez-Rodriguez, Lorna
9c04f571-8303-40d1-bb66-5e057a381bf3
Risch, Harvey A.
ffea3438-29d4-4cea-b784-11438a0428cf
Renner, Stefan P.
3d786f57-5820-4005-b7b2-c864ea0a29e0
Poole, Elizabeth M.
ae6d0b68-1a18-43b6-997c-67b3d9646c1f
Pike, Malcolm C.
4ace3b3a-923b-46c8-9ff3-79bb5297265f
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Pelttari, Liisa M.
abf40d24-3192-44f4-994d-fe1b9cedad00
Pejovic, Tanja
74afdf27-a8d3-4f63-877e-053cbac1d3d4
Paul, James
2f625e68-7c18-453b-8435-844efa1d6d2c
Orlow, Irene
53e1646d-28ee-4008-b15e-776cd982cb26
Zawiah Omar, Siti
4f5e28f5-18b1-4f21-99cb-35358c7dcbb8
Olson, Sara H.
90516ad2-df99-492f-9aa1-52c2f135d444
Odunsi, Kunle
554f7ad6-362f-4ba2-819c-624886800ed0
Nickels, Stefan
a8a8ceec-1812-4e1a-8437-7631fbcda1fa
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Ness, Roberta B.
259c7a43-1e15-463c-8986-cea037093745
Narod, Steven A.
6857472a-006c-4c96-8ad0-a130ae557511
Nakanishi, Toru
91fa4512-1dc5-4b55-8cc3-6c1608403479
Moysich, Kirsten B.
ffae45be-b72e-41d7-996a-fb5274800133
Monteiro, Alvaro N.A.
dcb07236-6485-4885-9621-c94d5cef1802
Moes-Sosnowska, Joanna
71ed82a2-9bc2-40a6-ba1a-a72986873f99
Modugno, Francesmary
a234d152-a897-42f8-8ea5-c04081310c3b
Menon, Usha
f0dd65de-11d4-489a-a468-9589bbe43969
McLaughlin, John R.
13ce5b18-8229-417a-9f3e-24107eba6051
McGuire, Valerie
4f8aa2d1-525a-4361-8bf1-e476b62b092b
Matsuo, Keitaro
3b0e7957-f27c-4c9e-acad-18992a61b5fa
Mat Adenan, Noor Azmi
cdf96d6c-8a32-4666-beed-466f388440d8
Massuger, Leon F.A.G
1de59f98-bf86-4922-ade9-c7a738ee3ad6
Lurie, Galina
b9d5f486-356a-44cc-b3e6-3661aef563eb
Lundvall, Lene
f7303090-7f8f-4676-92dd-9c3bccb43fdb
Lubiński, Jan
eb890453-eb1b-44c5-b90a-ad7661b85be0
Lissowska, Jolanta
720b22b2-0e76-454c-8397-99b42a4d8f64
Levine, Douglas A.
ddb85640-ee51-41bf-98d5-13fcb3f13e09
Leminen, Arto
3d2f76c7-85b0-43f2-aea7-2c7b8dfd2a67
Lee, Alice W.
62b90055-8c48-4d7a-b982-50efca2d622c
Le, Nhu D.
a1cf60be-f2a2-409c-bd22-4a3e0b22e847
Lambrechts, Sandrina
7e8a13ee-c6f7-4c92-b1fa-222f52a2264c
Lambrechts, Diether
5248cbcf-eb45-4a52-a9fd-fcc5305f3b39
Kupryjanczyk, Jolanta
709f6ba4-fe84-487e-a09d-14c0c2d0b015
Krakstad, Camilla
37bbd5a2-fa14-4ad0-addb-d0a925a55be6
Konecny, Gottfried E.
46e8e0e2-3bc7-4139-8b30-75d876dbe2b1
Krüger Kjaer, Susanne
8f584c3e-f144-490d-a5de-da8bdbcc3115
Kiemeney, Lambertus A.
a6af871e-f8d5-4a1f-a114-842b0f2a88e2
Kelemen, Linda E.
20d9f9ac-ec73-4832-8f28-61257497af0b
Keeney, Gary L.
d7507717-370d-45ea-a9dd-8153812b91a2
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Karevan, Rod
4530ec6c-2f0b-46fb-9f82-0968d2430eac
Kalli, Kimberly R.
e04250da-5809-4037-9eab-c2bc8b46f62c
Kajiyama, Hiroaki
c023b3c5-dff7-411c-be71-084548552616
Ji, Bu-Tian
9d34aa9f-407f-40d7-8262-4519de029504
Jensen, Allan
3363733f-fb36-403f-be87-2b5b56fef718
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Iversen, Edwin
8bee9de2-ad28-46b1-ad7e-6179a3aa426c
Hosono, Satoyo
68e71a98-1668-4813-bf99-cbe5907b3efc
Høgdall, Claus K.
b44e3a82-88dd-4f7d-84c8-07f45eec2702
Høgdall, Estrid
d8cfe122-fd87-477f-8c02-9215e7b7e0b0
Hoatlin, Maureen
a886d9e7-5982-4088-ae0e-10eb1204c968
Hillemanns, Peter
e79bf85f-e517-47a6-a591-e1133c5e0e3c
Heitz, Florian
18b5c90e-015e-4444-9069-5a1f4cdc223c
Hein, Rebecca
f05b8eee-adbe-472a-8324-0d9618c544f4
Harter, Philipp
63561bef-670b-4780-90e4-99d3159ca16f
Halle, Mari K.
3928409f-046a-4e49-9aa1-be6b1a9037ee
Hall, Per
38291830-47e9-48f8-8f76-dfd990e55fb6
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Gore, Martin
c38b4500-ccbd-4505-9c58-68c8b27b54f2
Goodman, Marc T.
fc194370-ee36-4bdf-91af-13a5a9cc0cfa
Giles, Graham G.
c7cc8232-9817-41fb-a46c-64c14f6233a5
Gentry-Maharaj, Aleksandra
0f54f5ac-d94d-421f-81ac-a27d08d58d91
Garcia-Closas, Montserrat
bd1054d7-f127-4fa8-b52e-67a352d29009
Flanagan, James M.
ac6487d1-96c1-4262-91aa-721afc62a357
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Ekici, Arif B.
44ca45c0-3a86-4a3d-9266-ef6c2b3007d3
Edwards, Robert
0692cce9-d3df-4391-99c7-ab0761b17e4c
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Dürst, Matthias
1b1600a6-8bbd-4e4c-85ad-47d6465c7b94
du Bois, Andreas
82b1a729-77c9-4dfc-9672-e135a36a1129
Dörk, Thilo
b644de98-231c-49da-a152-7e8de797b6b0
Doherty, Jennifer A.
a31196c0-a68d-4078-ba15-03fb907f81a1
Despierre, Evelyn
e4148297-1454-4c52-8ba8-47b24d430184
Dansonka-Mieszkowska, Agnieszka
0f7f959b-68e0-4a11-9515-ae3319dcf62f
Cybulski, Cezary
6c6cf54d-5e0e-4395-b8bb-7f1691a90e7f
Cramer, Daniel W.
9c40e027-08c3-4bf1-8c6e-39de9f11a620
Cook, Linda S.
57372664-7ec6-483f-835b-e6b3cd7db704
Chen, Xiaoqing
ee420c6c-2134-49d2-8238-514d837c725f
Charbonneau, Bridget
1f0a193e-3e06-4022-9811-78bb84611175
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
Campbell, Ian
4933e498-792b-4064-9ac8-edfa56713765
Butzow, Ralf
77e849a3-7e63-423f-bc1a-7bf95b2028d1
Bunker, Clareann H.
31f94be0-8b60-4793-8327-0452d60b6e15
Brueggmann, Doerthe
9f1f319b-7426-48d4-9189-8b7668d1b60a
Brown, Robert
dcb5c6ce-2410-4130-9ea0-d5935b8e1195
Brooks-Wilson, Angela
e591e81b-5d0a-49a7-b6ba-8025bade5514
Brinton, Louise A.
6611efb5-fd58-4eee-89c7-babe4190dfe8
Bogdanova, Natalia
787ed2dc-0af2-410d-bf0f-5fde3ed2980c
Block, Matthew S.
386abff2-d3a6-4b00-9750-472dabd0db34
Benjamin, Elizabeth
dcf412f7-34bc-4071-96dc-ecdea58e3db1
Beesley, Jonathan
0ec7ea7e-d634-48f5-9a1a-89158c82597d
Beckmann, Matthias W.
01050892-1f0b-4e97-a339-049930a46d01
Bandera, Elisa V.
4e52d275-b041-4f5f-a6af-a596ba0fcde1
Baglietto, Laura
509f481e-f606-4f82-a1e2-ced910886c68
Bacot, François
f6897349-5530-4f97-8890-bc7c7159c121
Armasu, Sebastian M.
c2a25532-9d11-4800-88ba-58faa995debf
Antonenkova, Natalia
a225af26-6132-4c47-8424-a1dfda09cfc6
Anton-Culver, Hoda
6d8396d5-8d76-4207-a8f1-5729d5f2d0de
Aben, Katja K.
4dc0ecc8-029d-4a01-8710-bf9755700169
Liang, Dong
26ed144c-88fc-48ac-9621-863d92589924
Wu, Xifeng
5413c3fa-0a9c-410a-b8f6-41a3a0cbe0ea
Lu, Karen
b545d035-58b7-45e0-86e2-e48cb43f27c1
Hildebrandt, Michelle A.T.
0ab4b8ef-a56d-4bb7-9f28-9f8e83a314ff
Schildkraut, Joellen M.
d52d66b9-4a15-48fd-97df-1bdc0696ea1a
Sellers, Thomas A.
af3ae8a7-365a-4b5c-a057-474380f575ab
Huntsman, David
d313b3d2-e655-45ba-961c-87900082f87e
Berchuck, Andrew
1e234fbd-4421-49d8-9fbf-b19098d71434
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Gayther, Simon A.
5333cc14-fc1e-4517-9808-be39b0fb009c
Pharoah, Paul D.P.
75503648-dfdc-4da1-93c9-26fa44dec680
Laird, Peter W.
e957358b-ac1e-4508-a324-b39944b4d177
Goode, Ellen L.
e57c9220-6e9e-42d4-bc4c-6f4571505a64
Leigh Pearce, Celeste
65d0d7fa-298c-422c-8a62-dac51fd86395
Shen, Hui
0ab92c75-afbc-4e65-a033-139d98b1c38f
Fridley, Brooke L.
d659bf17-d796-4e8f-9af5-2dff1c11deaf
Song, Honglin
90088f14-dc56-4280-83e3-71ad1744858d
Lawrenson, Kate
b1787caf-36bc-4378-a1f3-11545308f6f1
Cunningham, Julie M.
6181118b-0b2c-4af9-8d8e-241b76808ca8
Ramus, Susan J.
f2a91d0b-8aab-4e57-b49f-7637767b4f57
Cicek, Mine S.
b8d7736c-dc66-491b-85ed-898847799f1c
Tyrer, Jonathan
2c15ee61-c6e4-4c0a-9190-b0592bce73cc
Stram, Douglas
75fd6341-cd22-455c-8384-ee924bbcbae3
Larson, Melissa C.
c1819763-4dc3-4514-91bf-97c2cfbe6692
Köbel, Martin
34633857-78fe-445d-902a-4659f2f5fb9e
Ziogas, Argyrios
786f0e72-cf35-4301-805e-6128295e4a4f
Zheng, Wei
e8338ae7-b60e-46dd-bf1b-7648891c6fe4
Yang, Hannah P.
3c435365-a2eb-486d-8d4d-e638c486753f
Wu, Anna H.
a657c0a4-2887-4b9c-a018-a795197920e3
Wozniak, Eva L.
df1ab03e-1f87-4ec4-b7d4-97ff1f3ed825
Ling Woo, Yin
41638407-4044-4380-8161-81ab5825c584
Winterhoff, Boris
e91dfe8d-2f46-4480-8d5d-b49d5bea58cf
Wik, Elisabeth
1966758b-48f8-4bff-a8d9-be039f5a2b64
Whittemore, Alice S.
7d313f5d-6286-49a8-acb7-4e6bfafb117c
Wentzensen, Nicolas
43ddba47-f169-466d-b6aa-c2f5a20e9753
Palmieri Weber, Rachel
756bbe18-0f56-4cea-9873-52863bc273e0
Vitonis, Allison F.
20fb802a-cd81-49bf-8e98-44c35da4d35f
Vincent, Daniel
36e0c2d5-2536-4040-a97d-4f6ec074c731
Vierkant, Robert A.
2c236081-4238-4d9a-b160-f2b3d83a10f6
Vergote, Ignace
119d04aa-b069-43e7-8fef-3b3218c13e86
Van Den Berg, David
643617d5-b80b-464d-b64e-6b49afc263ac
Van Altena, Anne M.
70e14f69-ca1d-4e1d-b6b4-42dc1965607a
Tworoger, Shelley S.
7016b048-06b3-43dd-a660-2bf19b34c3c1
Thompson, Pamela J.
69df292d-f664-42f0-aec1-58d0cab4962a
Tessier, Daniel C.
ffa92c90-84dd-4328-9a3b-b5cc9b6bedef
Terry, Kathryn L.
e1358eae-c105-4a69-b240-c248939d8bdf
Teo, Soo-Hwang
56e60db6-a62d-4c7d-a63b-8245ea786c42
Templeman, Claire
27978818-32b4-424b-ac51-bb2acff915ec
Stram, Daniel O.
170b190f-c863-4768-9966-9cd43953ec81
Southey, Melissa C.
56062dff-748c-47e4-99f5-044cff9da594
Sieh, Weiva
9d5bdd00-daee-4ad2-a93c-cabf9010a00d
Siddiqui, Nadeem
96d263e8-0f61-46e9-86a8-a13e622dc450
Shvetsov, Yurii B.
7c68801c-4e42-4cee-9e0c-0ee1e4a1969f
Shu, Xiao-Ou
77f6b7c1-6f68-4030-8f69-f6003269d5da
Shridhar, Viji
a0a96a4c-c52f-4ecc-98b8-183ac0aa749c
Wang-Gohrke, Shan
5bce864c-5f22-44d2-b5a0-b53a3e7abe8e
Severi, Gianluca
e0a9b779-4324-434a-90ac-ecef87ed04ed
Schwaab, Ira
6b723711-4958-47a3-9338-73d587dac1e2
Salvesen, Helga B.
f6728260-5c3a-4714-b78c-fd741f9755c2
Rzepecka, Iwona K.
9cba996d-4e8e-4f1b-9117-3130aa6c445e
Runnebaum, Ingo B.
a16e9d3c-66b3-41a7-80a1-5663f75f52da
Anne Rossing, Mary
18f7ab9e-1570-4dea-a065-258b492f594c
Rodriguez-Rodriguez, Lorna
9c04f571-8303-40d1-bb66-5e057a381bf3
Risch, Harvey A.
ffea3438-29d4-4cea-b784-11438a0428cf
Renner, Stefan P.
3d786f57-5820-4005-b7b2-c864ea0a29e0
Poole, Elizabeth M.
ae6d0b68-1a18-43b6-997c-67b3d9646c1f
Pike, Malcolm C.
4ace3b3a-923b-46c8-9ff3-79bb5297265f
Phelan, Catherine M.
0692189d-5402-41da-a627-acc6ba0c6505
Pelttari, Liisa M.
abf40d24-3192-44f4-994d-fe1b9cedad00
Pejovic, Tanja
74afdf27-a8d3-4f63-877e-053cbac1d3d4
Paul, James
2f625e68-7c18-453b-8435-844efa1d6d2c
Orlow, Irene
53e1646d-28ee-4008-b15e-776cd982cb26
Zawiah Omar, Siti
4f5e28f5-18b1-4f21-99cb-35358c7dcbb8
Olson, Sara H.
90516ad2-df99-492f-9aa1-52c2f135d444
Odunsi, Kunle
554f7ad6-362f-4ba2-819c-624886800ed0
Nickels, Stefan
a8a8ceec-1812-4e1a-8437-7631fbcda1fa
Nevanlinna, Heli
69be7a44-2abf-4504-a47b-a50b6723701b
Ness, Roberta B.
259c7a43-1e15-463c-8986-cea037093745
Narod, Steven A.
6857472a-006c-4c96-8ad0-a130ae557511
Nakanishi, Toru
91fa4512-1dc5-4b55-8cc3-6c1608403479
Moysich, Kirsten B.
ffae45be-b72e-41d7-996a-fb5274800133
Monteiro, Alvaro N.A.
dcb07236-6485-4885-9621-c94d5cef1802
Moes-Sosnowska, Joanna
71ed82a2-9bc2-40a6-ba1a-a72986873f99
Modugno, Francesmary
a234d152-a897-42f8-8ea5-c04081310c3b
Menon, Usha
f0dd65de-11d4-489a-a468-9589bbe43969
McLaughlin, John R.
13ce5b18-8229-417a-9f3e-24107eba6051
McGuire, Valerie
4f8aa2d1-525a-4361-8bf1-e476b62b092b
Matsuo, Keitaro
3b0e7957-f27c-4c9e-acad-18992a61b5fa
Mat Adenan, Noor Azmi
cdf96d6c-8a32-4666-beed-466f388440d8
Massuger, Leon F.A.G
1de59f98-bf86-4922-ade9-c7a738ee3ad6
Lurie, Galina
b9d5f486-356a-44cc-b3e6-3661aef563eb
Lundvall, Lene
f7303090-7f8f-4676-92dd-9c3bccb43fdb
Lubiński, Jan
eb890453-eb1b-44c5-b90a-ad7661b85be0
Lissowska, Jolanta
720b22b2-0e76-454c-8397-99b42a4d8f64
Levine, Douglas A.
ddb85640-ee51-41bf-98d5-13fcb3f13e09
Leminen, Arto
3d2f76c7-85b0-43f2-aea7-2c7b8dfd2a67
Lee, Alice W.
62b90055-8c48-4d7a-b982-50efca2d622c
Le, Nhu D.
a1cf60be-f2a2-409c-bd22-4a3e0b22e847
Lambrechts, Sandrina
7e8a13ee-c6f7-4c92-b1fa-222f52a2264c
Lambrechts, Diether
5248cbcf-eb45-4a52-a9fd-fcc5305f3b39
Kupryjanczyk, Jolanta
709f6ba4-fe84-487e-a09d-14c0c2d0b015
Krakstad, Camilla
37bbd5a2-fa14-4ad0-addb-d0a925a55be6
Konecny, Gottfried E.
46e8e0e2-3bc7-4139-8b30-75d876dbe2b1
Krüger Kjaer, Susanne
8f584c3e-f144-490d-a5de-da8bdbcc3115
Kiemeney, Lambertus A.
a6af871e-f8d5-4a1f-a114-842b0f2a88e2
Kelemen, Linda E.
20d9f9ac-ec73-4832-8f28-61257497af0b
Keeney, Gary L.
d7507717-370d-45ea-a9dd-8153812b91a2
Karlan, Beth Y.
0a74d552-f43d-4670-bc0c-0f860d55b15e
Karevan, Rod
4530ec6c-2f0b-46fb-9f82-0968d2430eac
Kalli, Kimberly R.
e04250da-5809-4037-9eab-c2bc8b46f62c
Kajiyama, Hiroaki
c023b3c5-dff7-411c-be71-084548552616
Ji, Bu-Tian
9d34aa9f-407f-40d7-8262-4519de029504
Jensen, Allan
3363733f-fb36-403f-be87-2b5b56fef718
Jakubowska, Anna
ecdb73a5-85f8-49ba-b03e-dcf4b559d5b1
Iversen, Edwin
8bee9de2-ad28-46b1-ad7e-6179a3aa426c
Hosono, Satoyo
68e71a98-1668-4813-bf99-cbe5907b3efc
Høgdall, Claus K.
b44e3a82-88dd-4f7d-84c8-07f45eec2702
Høgdall, Estrid
d8cfe122-fd87-477f-8c02-9215e7b7e0b0
Hoatlin, Maureen
a886d9e7-5982-4088-ae0e-10eb1204c968
Hillemanns, Peter
e79bf85f-e517-47a6-a591-e1133c5e0e3c
Heitz, Florian
18b5c90e-015e-4444-9069-5a1f4cdc223c
Hein, Rebecca
f05b8eee-adbe-472a-8324-0d9618c544f4
Harter, Philipp
63561bef-670b-4780-90e4-99d3159ca16f
Halle, Mari K.
3928409f-046a-4e49-9aa1-be6b1a9037ee
Hall, Per
38291830-47e9-48f8-8f76-dfd990e55fb6
Gronwald, Jacek
4a0117ac-84f8-4351-a97d-637a60db25f6
Gore, Martin
c38b4500-ccbd-4505-9c58-68c8b27b54f2
Goodman, Marc T.
fc194370-ee36-4bdf-91af-13a5a9cc0cfa
Giles, Graham G.
c7cc8232-9817-41fb-a46c-64c14f6233a5
Gentry-Maharaj, Aleksandra
0f54f5ac-d94d-421f-81ac-a27d08d58d91
Garcia-Closas, Montserrat
bd1054d7-f127-4fa8-b52e-67a352d29009
Flanagan, James M.
ac6487d1-96c1-4262-91aa-721afc62a357
Fasching, Peter A.
28905b56-c431-479b-8687-98d5858e04e9
Ekici, Arif B.
44ca45c0-3a86-4a3d-9266-ef6c2b3007d3
Edwards, Robert
0692cce9-d3df-4391-99c7-ab0761b17e4c
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Easton, Douglas F.
2661cf5e-8fc6-4f1d-b27a-e60cac8c8819
Dürst, Matthias
1b1600a6-8bbd-4e4c-85ad-47d6465c7b94
du Bois, Andreas
82b1a729-77c9-4dfc-9672-e135a36a1129
Dörk, Thilo
b644de98-231c-49da-a152-7e8de797b6b0
Doherty, Jennifer A.
a31196c0-a68d-4078-ba15-03fb907f81a1
Despierre, Evelyn
e4148297-1454-4c52-8ba8-47b24d430184
Dansonka-Mieszkowska, Agnieszka
0f7f959b-68e0-4a11-9515-ae3319dcf62f
Cybulski, Cezary
6c6cf54d-5e0e-4395-b8bb-7f1691a90e7f
Cramer, Daniel W.
9c40e027-08c3-4bf1-8c6e-39de9f11a620
Cook, Linda S.
57372664-7ec6-483f-835b-e6b3cd7db704
Chen, Xiaoqing
ee420c6c-2134-49d2-8238-514d837c725f
Charbonneau, Bridget
1f0a193e-3e06-4022-9811-78bb84611175
Chang-Claude, Jenny
cf472d49-8420-41ff-8a38-b0148f0a7cae
Campbell, Ian
4933e498-792b-4064-9ac8-edfa56713765
Butzow, Ralf
77e849a3-7e63-423f-bc1a-7bf95b2028d1
Bunker, Clareann H.
31f94be0-8b60-4793-8327-0452d60b6e15
Brueggmann, Doerthe
9f1f319b-7426-48d4-9189-8b7668d1b60a
Brown, Robert
dcb5c6ce-2410-4130-9ea0-d5935b8e1195
Brooks-Wilson, Angela
e591e81b-5d0a-49a7-b6ba-8025bade5514
Brinton, Louise A.
6611efb5-fd58-4eee-89c7-babe4190dfe8
Bogdanova, Natalia
787ed2dc-0af2-410d-bf0f-5fde3ed2980c
Block, Matthew S.
386abff2-d3a6-4b00-9750-472dabd0db34
Benjamin, Elizabeth
dcf412f7-34bc-4071-96dc-ecdea58e3db1
Beesley, Jonathan
0ec7ea7e-d634-48f5-9a1a-89158c82597d
Beckmann, Matthias W.
01050892-1f0b-4e97-a339-049930a46d01
Bandera, Elisa V.
4e52d275-b041-4f5f-a6af-a596ba0fcde1
Baglietto, Laura
509f481e-f606-4f82-a1e2-ced910886c68
Bacot, François
f6897349-5530-4f97-8890-bc7c7159c121
Armasu, Sebastian M.
c2a25532-9d11-4800-88ba-58faa995debf
Antonenkova, Natalia
a225af26-6132-4c47-8424-a1dfda09cfc6
Anton-Culver, Hoda
6d8396d5-8d76-4207-a8f1-5729d5f2d0de
Aben, Katja K.
4dc0ecc8-029d-4a01-8710-bf9755700169
Liang, Dong
26ed144c-88fc-48ac-9621-863d92589924
Wu, Xifeng
5413c3fa-0a9c-410a-b8f6-41a3a0cbe0ea
Lu, Karen
b545d035-58b7-45e0-86e2-e48cb43f27c1
Hildebrandt, Michelle A.T.
0ab4b8ef-a56d-4bb7-9f28-9f8e83a314ff
Schildkraut, Joellen M.
d52d66b9-4a15-48fd-97df-1bdc0696ea1a
Sellers, Thomas A.
af3ae8a7-365a-4b5c-a057-474380f575ab
Huntsman, David
d313b3d2-e655-45ba-961c-87900082f87e
Berchuck, Andrew
1e234fbd-4421-49d8-9fbf-b19098d71434
Chenevix-Trench, Georgia
7d222914-c6e5-47b8-9022-5874b7c82a3e
Gayther, Simon A.
5333cc14-fc1e-4517-9808-be39b0fb009c
Pharoah, Paul D.P.
75503648-dfdc-4da1-93c9-26fa44dec680
Laird, Peter W.
e957358b-ac1e-4508-a324-b39944b4d177
Goode, Ellen L.
e57c9220-6e9e-42d4-bc4c-6f4571505a64
Leigh Pearce, Celeste
65d0d7fa-298c-422c-8a62-dac51fd86395

Shen, Hui, Fridley, Brooke L. and Song, Honglin et al. (2013) Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer. Nature Communications, 4, 1628-[10pp]. (doi:10.1038/ncomms2629). (PMID:23535649)

Record type: Article

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

Text
__userfiles.soton.ac.uk_Users_slb1_mydesktop_ncomms2629.pdf - Other
Available under License Other.
Download (1MB)

More information

Accepted/In Press date: 21 February 2013
Published date: 27 March 2013
Keywords: biological sciences, cancer, genetics
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 382847
URI: http://eprints.soton.ac.uk/id/eprint/382847
PURE UUID: 5d166441-7b85-4ca7-87d7-379faae84e4c
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

Catalogue record

Date deposited: 13 Oct 2015 08:44
Last modified: 15 Mar 2024 02:40

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×