Profiling of linker histone variants in ovarian cancer.
Profiling of linker histone variants in ovarian cancer.
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DOI：
10.2741/3934
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
Medrzycki M;Zhang Y;McDonald JF;Fan Y
H1接头组蛋白在促进染色质高级折叠中起关键作用。新出现的证据表明，H1及其多种变体是调节染色质功能和基因表达的重要表观遗传因素。卵巢癌是一种毁灭性的疾病，由于其预后差和早期诊断困难，在所有妇女癌症死亡中排名第五。虽然卵巢癌的表观遗传学改变被普遍认可，但H1的作用尚未被探索。在这里，我们使用定量RT-PCR分析，系统地研究了7个H1基因在33人卵巢上皮性肿瘤中的表达。与良性腺瘤相比，恶性腺瘤中H1.3的表达显著增加，而H1°、H1.1、H1.4和H1 x的表达显著减少。引人注目的是，卵巢腺癌和腺瘤表现出特征性的表达模式，7 H1基因在肿瘤样品中的表达谱区分腺癌与腺瘤具有高准确性。这些发现表明，H1变体的表达受到精细调控，可能作为卵巢癌的潜在表观遗传生物标志物。
H1 linker histones play a key role in facilitating higher order chromatin folding. Emerging evidence suggests that H1 and its multiple variants are important epigenetic factors in modulating chromatin function and gene expression. Ovarian cancer is a devastating disease, ranking the fifth leading cause of all women cancer death due to its poor prognosis and difficulty in early diagnosis. Although epigenetic alterations in ovarian cancers are being appreciated in general, the role of H1 has not been explored. Here, using quantitative RT-PCR assays, we systematically examined the expression of 7 H1 genes in 33 human epithelial ovarian tumors. Whereas the expression of H1.3 was markedly increased, the expression of H1°, H1.1, H1.4 and H1x were significantly reduced in malignant adenocarcinomas compared with benign adenomas. Strikingly, ovarian adenocarcinomas and adenomas exhibited characteristic expression patterns, and expression profiling of 7 H1 genes in tumor samples discriminated adenocarcinomas vs. adenomas with high accuracy. These findings indicate that the expression of H1 variants is exquisitely regulated and may serve as potential epigenetic biomarkers for ovarian cancer.
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