DNA methylation profile at the DNMT3L promoter: a potential biomarker for cervical cancer.
DNA methylation profile at the DNMT3L promoter: a potential biomarker for cervical cancer.
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DOI：
10.4161/epi.2.2.3692
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发表时间：
2007-04
期刊：
影响因子：
3.7
通讯作者：
Khosla S
中科院分区：
文献类型：
--
作者：
Gokul G;Gautami B;Malathi S;Sowjanya AP;Poli UR;Jain M;Ramakrishna G;Khosla S
表观遗传事件在癌症发展过程中起着重要作用。这从几乎所有癌症类型都显示异常DNA甲基化的事实中显而易见。这些异常的DNA甲基化水平不仅限于少数基因，而是影响整个基因组。以前的研究表明，全基因组DNA低甲基化和基因特异性高甲基化是大多数癌症的标志。像DNA甲基转移酶这样的分子是表观遗传重编程的效应子。在本研究中，我们已经研究了重编程基因本身经历表观遗传修饰的可能性，反映了癌症发展过程中转录状态的变化。在一些重编程分子的启动子处进行正常和宫颈癌样品之间的DNA甲基化状态的比较。我们的研究揭示了DNMT3L启动子内具有统计学意义的DNA甲基化差异。在分析的15个宫颈癌样本中，发现DNMT3L启动子是从头DNA甲基转移酶DNMT3A和DNMT3B的调节剂，其DNA甲基化程度不同。本研究强调了DNMT3L启动子DNA甲基化谱的重要性，不仅作为宫颈癌（全球女性第二大常见癌症）的有希望的生物标志物，而且还提供了对DNMT3L在癌症发展中可能作用的见解。
Epigenetic events play a prominent role during cancer development. This is evident from the fact that almost all cancer types show aberrant DNA methylation. These abnormal DNA methylation levels are not restricted to just a few genes but affect the whole genome. Previous studies have shown genome-wide DNA hypomethylation and gene-specific hypermethylation to be a hallmark of most cancers. Molecules like DNA methyltransferase act as effectors of epigenetic reprogramming. In the present study we have examined the possibility that the reprogramming genes themselves undergo epigenetic modifications reflecting their changed transcriptional status during cancer development. Comparison of DNA methylation status between the normal and cervical cancer samples was carried out at the promoters of a few reprogramming molecules. Our study revealed statistically significant DNA methylation differences within the promoter of DNMT3L. A regulator of de novo DNA methyltransferases DNMT3A and DNMT3B, DNMT3L promoter was found to have lost DNA methylation to varying levels in 14 out of 15 cancer cervix samples analysed. The present study highlights the importance of DNA methylation profile at DNMT3L promoter not only as a promising biomarker for cervical cancer, which is the second most common cancer among women worldwide, but also provides insight into the possible role of DNMT3L in cancer development.