Background

Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality. In addition to having genetic causes, cancer can also be considered an epigenetic disease. DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor. In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma (PDAC), the epigenetic changes play a significant role.

Data sources

Relevant studies for this review were derived via an extensive literature search in PubMed via using various keywords such as pancreatic ductal adenocarcinoma, precancerous lesions, methylation profile, epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest. The literature search was intensively done considering a time frame of 20 years (1998–2018).

Result

In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions (pancreatic intra-epithelial neoplasia, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm and chronic pancreatitis) and PDAC along with the potential biomarkers. We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC. A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC (ppENK, APC, p14/5/16/17, hMLH1 and MGMT) are also documented. We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy. Epigenetic inactivation occurs by hypermethylation of CpG islands in the promoter regions of tumor suppressor genes. We listed all hyper- and hypomethylation of CpG islands of several genes in PDAC including its precancerous lesions.

Conclusions

The concept of the review would help to understand their biological effects, and to determine whether they may be successfully combined with other epigenetic drugs. However, we need to continue our research to develop more specific DNA-demethylating agents, which are the targets for hypermethylated CpG methylation sites.

中文翻译：

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胰腺导管腺癌及其癌前病变的差异甲基化景观。

背景

胰腺癌是最致命的疾病之一，其发病率几乎等于死亡率。除了具有遗传原因外，癌症也可以被视为表观遗传疾病。DNA甲基化是主要的表观遗传修饰，异常DNA甲基化的模式被认为是人类肿瘤的共同特征。在胰腺癌从癌前病变到胰腺导管腺癌（PDAC）的多阶段癌变中，表观遗传变化起着重要作用。

数据源

这篇综述的相关研究是通过在PubMed中进行广泛的文献检索而得出的，其中使用了各种关键词，例如胰腺导管腺癌，癌前病变，甲基化谱，与我们感兴趣的相关领域直接或紧密相关的表观遗传标记。考虑20年（1998-2018年）的时间框架，对文献进行了深入研究。

结果

在这篇综述中，我们强调了癌前PDAC病变（胰腺上皮内瘤变，导管内乳头状粘液性肿瘤，粘液性囊性肿瘤和慢性胰腺炎）的甲基化和甲基化过低，以及潜在的生物标志物。我们还实现了早期表观遗传驱动程序，该驱动程序导致从癌前病变发展为PDAC。一堆表观遗传驱动基因导致癌前病变发展为PDAC（ppENK，APC，p14 / 5/16/17，hMLH1和MGMT）也已记录在案。我们总结了这些观察结果在PDAC的治疗和诊断中的重要性，从而确定了表观遗传生物标志物在表观遗传靶向治疗中的潜在用途。表观遗传失活通过肿瘤抑制基因启动子区域中CpG岛的超甲基化而发生。我们列出了PDAC中几个基因的CpG岛的所有高甲基化和低甲基化，包括其癌前病变。

结论

审查的概念将有助于了解它们的生物学效应，并确定它们是否可以与其他表观遗传药物成功结合。但是，我们需要继续研究以开发更特异性的DNA脱甲基剂，它们是超甲基化CpG甲基化位点的目标。