Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Cancer Metastasis Rev. 2010 Mar;29(1):95-107. doi: 10.1007/s10555-010-9203-x.
DNA methylation as part of the epigenetic gene-silencing complex is a universal occurring change in lung cancer. Numerous studies investigated methylation of specific genes in primary tumors, in serum or plasma samples, and in specimens from the aerodigestive tract epithelium of lung cancer patients. In most studies, single genes or small numbers of genes were analyzed. Moreover, it has been observed that methylation of certain genes can already be detected in samples from the upper aerodigestive tract epithelium of cancer-free heavy smokers. These findings indicated that methylation of certain genes may be a useful biomarker for prognosis, disease recurrence, early detection, and lung cancer risk assessment. So far, several genes were identified which seem to be of worse prognostic relevance when they were found to be methylated. In addition, it has been shown that a panel of markers may be relevant to predict disease recurrence after surgery. In comparison to analysis of single or small numbers of genes, methods for genome-wide detection of methylation were developed recently. These approaches are focused on either pharmacological re-activation of methylated genes followed by expression microarray analysis or on microarray analysis of sodium bisulfite-treated or affinity-enriched methylated DNA sequences. With currently available methods for the simultaneous detection of methylation, up to 28,000 CpG islands can be analyzed. Overall, we are just at the beginning of translating these findings into the clinic and there is hope that future patients will benefit from these results.
DNA 甲基化是表观遗传基因沉默复合物的一部分，是肺癌中普遍存在的变化。许多研究调查了原发性肿瘤、血清或血浆样本以及肺癌患者的呼吸道上皮样本中特定基因的甲基化。在大多数研究中，仅分析了单个基因或少数几个基因。此外，人们观察到，在无癌症的重度吸烟者的上呼吸道上皮样本中，某些基因的甲基化已经可以检测到。这些发现表明，某些基因的甲基化可能是预后、疾病复发、早期检测和肺癌风险评估的有用生物标志物。到目前为止，已经确定了几个似乎与预后相关的基因，当它们被发现甲基化时。此外，已经表明一组标记物可能与预测手术后疾病复发相关。与分析单个或少数几个基因相比，最近开发了用于全基因组检测甲基化的方法。这些方法主要集中在药物重新激活甲基化基因，然后进行表达微阵列分析，或对亚硫酸氢盐处理或亲和富集的甲基化 DNA 序列进行微阵列分析。目前可用于同时检测甲基化的方法，最多可以分析 28000 个 CpG 岛。总的来说，我们刚刚开始将这些发现转化为临床实践，希望未来的患者能够从这些结果中受益。
