DNA 甲基化对于染色质结构、转录调控和基因组稳定性至关重要，从而定义细胞身份。 CpG 丰富区域的异常高甲基化在癌症中很常见，会影响基因表达。然而，个体表观遗传修饰对肿瘤发生的具体贡献仍在研究中。在肝细胞癌 (HCC) 中，与其他肿瘤类型一样，DNA 甲基化改变也被记录下来。我们的目的是鉴定 HCC 中高甲基化的 CpG，评估它们在其他肿瘤类型中的特异性，并研究它们对基因表达的影响。为此，我们分析了 HCC、其他肝脏疾病和 27 种肿瘤类型的公共甲基化组以及 TCGA-LIHC 和 GTEx 的表达数据。这项研究鉴定出与对照肝组织相比，HCC 中的 39 个 CpG 位点高度甲基化，并且位于启动子、基因体和基因间 CpG 岛内。值得注意的是，这些 CpG 在健康肝组织和其他正常组织中主要未甲基化。与其他 27 种肿瘤的比较分析揭示了常见和 HCC 特异性的高甲基化 CpG。有趣的是，HCC 高甲基化基因在不同的健康组织中表现出最小的表达，而在相应肿瘤中的表达水平略有变化。这些发现证实了先前的证据，即 DNA 高甲基化对癌症基因表达调控的影响有限。它还强调了在癌发生过程中允许在正常不表达的基因中选择组织特异性甲基化标记的机制的存在。总的来说，我们的研究有助于证明癌症表观遗传学的复杂性，强调需要更好地理解 DNA 甲基化、基因表达动态和肿瘤发生之间的相互作用。© 2024。作者。

DNA methylation is crucial for chromatin structure, transcription regulation and genome stability, defining cellular identity. Aberrant hypermethylation of CpG-rich regions is common in cancer, influencing gene expression. However, the specific contributions of individual epigenetic modifications to tumorigenesis remain under investigation. In hepatocellular carcinoma (HCC), DNA methylation alterations are documented as in other tumor types. We aimed to identify hypermethylated CpGs in HCC, assess their specificity across other tumor types, and investigate their impact on gene expression. To this end, public methylomes from HCC, other liver diseases, and 27 tumor types as well as expression data from TCGA-LIHC and GTEx were analyzed. This study identified 39 CpG sites that were hypermethylated in HCC compared to control liver tissue, and were located within promoter, gene bodies, and intergenic CpG islands. Notably, these CpGs were predominantly unmethylated in healthy liver tissue and other normal tissues. Comparative analysis with 27 other tumors revealed both common and HCC-specific hypermethylated CpGs. Interestingly, the HCC-hypermethylated genes showed minimal expression in the different healthy tissues, with marginal changes in the level of expression in the corresponding tumors. These findings confirm previous evidence on the limited influence of DNA hypermethylation on gene expression regulation in cancer. It also highlights the existence of mechanisms that allow the selection of tissue-specific methylation marks in normally unexpressed genes during carcinogenesis. Overall, our study contributes to demonstrate the complexity of cancer epigenetics, emphasizing the need of better understanding the interplay between DNA methylation, gene expression dynamics, and tumorigenesis.© 2024. The Author(s).