DNA甲基化是一个调节基因表达的表观遗传特征，其失调在癌症中观察到。我们先前在结肠癌中鉴定了与神经相关的DNA甲基化指纹，其中大部分顶级高甲基化和下调的基因在神经系统中有已知功能。为了评估这一特征在癌症发生中的存在和相关性，我们考虑了The Cancer Genome Atlas（TCGA）中可用的16种实体癌症类型。所有测试的癌症都显示出在高甲基化基因中神经相关基因的显著富集。这一特征已经存在于两种癌前组织类型，并且不能通过潜在混杂因素，如双价状态或肿瘤纯度来解释。对结肠癌中的神经相关DNA甲基化特征进行进一步的表征显示，这些基因在神经分化过程中过表达。最后，上游调控因子的分析确定了RE1寂静转录因子（REST）作为该DNA甲基化特征的潜在调节因子。我们的研究确认了神经相关DNA甲基化指纹在各种癌症中的存在，这些基因与神经分化有关，并指出REST可能是这一机制的调节者。我们提出，这一指纹表明DNA甲基化参与了癌细胞中神经干细胞特性的保留。© 2023. BioMed Central Ltd., part of Springer Nature.

DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA).All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature.Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.© 2023. BioMed Central Ltd., part of Springer Nature.