Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Dis Markers. 2013;34(2):93-104. doi: 10.3233/DMA-120948.
The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site in TMEM25 in 69.2% (92/133) tumours analysed. Furthermore, the expression of TMEM25 was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation of TMEM25 and TMEM25 down-regulated expression was observed. Our results suggest that epigenetic down-regulation of TMEM25 is cancer-related; we thus suggest that TMEM25 hypermethylation might play a significant role in altering expression of this gene in colorectal cancer.
鉴定结直肠癌发生过程中涉及的新基因对于早期诊断、应用新的治疗策略和监测疾病复发具有重要的临床意义，以便降低疾病发病率和死亡率。CpG 岛过度甲基化导致的基因沉默是癌症发生过程中的一个主要表观遗传机制。在我们的研究中，我们旨在鉴定和验证结直肠癌中具有肿瘤特异性 DNA 甲基化模式的新基因。我们进行了全基因组甲基化扫描，发现与健康结肠黏膜相比，在肿瘤中存在多个可能的候选基因发生过度甲基化。通过对包括 133 例结直肠癌样本的一组样本进行甲基化特异性高分辨率熔解分析，我们能够在分析的 69.2%（92/133）肿瘤中确认 TMEM25 中发生改变的 CpG 位点。此外，发现 TMEM25 的表达在肿瘤组织中显著降低。TMEM25 的过度甲基化与 TMEM25 下调表达之间存在反相关关系。我们的研究结果表明，TMEM25 的表观遗传下调与癌症相关；因此，我们建议 TMEM25 过度甲基化可能在改变结直肠癌中该基因的表达方面发挥重要作用。
