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.
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DOI：
10.1038/ncomms2629
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发表时间：
2013
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
HNF 1B在透明细胞上皮性卵巢癌中过表达，我们观察到浆液性上皮性卵巢癌中的表观遗传沉默，这使我们假设该基因的变异与上皮性卵巢癌的风险差异相关，根据组织学亚型。在这里，我们全面绘制了HNF 1B变异与上皮性卵巢癌风险的关系，并分析了不同组织学亚型的DNA甲基化和表达谱。不同的单核苷酸多态性与浸润性浆液性（rs7405776比值比（OR）=1.13，P=3.1 × 10−10）和透明细胞（rs 11651755 OR=0.77，P=1.6 × 10−8）上皮性卵巢癌相关。在这些肿瘤中，浆液性亚型的风险等位基因与较高的HNF 1B启动子甲基化相关。未甲基化的表达HNF 1B主要存在于透明细胞肿瘤中，与影响整个基因组中许多其他启动子的CpG岛甲基化表型一致。HNF 1B的不同变体与浆液性和透明细胞上皮性卵巢癌的风险相关; DNA甲基化和表达模式在这些亚型之间也有显著差异。这些发现强调了驱动不同上皮性卵巢癌组织学亚型的不同机制。本文的在线版本（doi：10.1038/ncomms 2629）包含补充材料，授权用户可以使用。HNF 1B在卵巢癌的透明细胞亚型中过表达，而在浆液性亚型中表观遗传学沉默。皮尔斯及其同事现在表明，HNF 1B的遗传变异与这两种癌症亚型的发生风险存在差异，可能是通过表观遗传机制。本文的在线版本（doi：10.1038/ncomms 2629）包含补充材料，授权用户可以使用。
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. The online version of this article (doi:10.1038/ncomms2629) contains supplementary material, which is available to authorized users. HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism. The online version of this article (doi:10.1038/ncomms2629) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
DOI：
10.1097/pas.0b013e3181cf3d79
发表时间：
2010-03
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Kurman RJ;Shih IeM
通讯作者：
Shih IeM
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
5
作者：
Risch, HA;Marrett, LD;Howe, GR
通讯作者：
Howe, GR