Virmani Arvind K, Tsou Jeffrey A, Siegmund Kimberly D, Shen Linda Y C, Long Tiffany I, Laird Peter W, Gazdar Adi F, Laird-Offringa Ite A
Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9593, USA.
Cancer Epidemiol Biomarkers Prev. 2002 Mar;11(3):291-7.
Recent analyses of global and gene-specific methylation patterns in cancer cells have suggested that cancers from different organs demonstrate distinct patterns of CpG island hypermethylation. Although certain CpG islands are frequently methylated in many different kinds of cancer, others are methylated only in specific tumor types. Because distinct patterns of CpG island hypermethylation can be seen in tumors from different organs, it seems likely that histological subtypes of cancer within a given organ may exhibit distinct methylation patterns as well. The goal of our study was to determine whether the patterns of CpG island hypermethylation could be used to distinguish between different histological subtypes of lung cancer. We analyzed the methylation status of 23 loci in 91 lung cancer cell lines using the quantitative real-time PCR method MethyLight. Genes PTGS2 (COX2), CALCA, MTHFR, ESR1, MGMT, MYOD1, and APC showed statistically significant differences in the level of CpG island methylation between small cell lung cancer (SCLC) and non-small cell lung cancer cell lines (NSCLC). Hierarchical clustering using a panel consisting of these seven loci yielded two major groups, one of which contained 78% of the SCLC lines. Within this group, a large cluster consisted almost exclusively of SCLC cell lines. Our results show that DNA methylation patterns differ between NSCLC and SCLC cell lines and suggest that these patterns could be developed into a powerful molecular marker to achieve accurate diagnosis of lung cancer.
近期对癌细胞中全球及基因特异性甲基化模式的分析表明，来自不同器官的癌症呈现出不同的CpG岛高甲基化模式。尽管某些CpG岛在许多不同类型的癌症中经常发生甲基化，但其他一些CpG岛仅在特定肿瘤类型中发生甲基化。由于在不同器官的肿瘤中可以看到不同的CpG岛高甲基化模式，那么给定器官内癌症的组织学亚型似乎也可能呈现出不同的甲基化模式。我们研究的目的是确定CpG岛高甲基化模式是否可用于区分肺癌的不同组织学亚型。我们使用定量实时PCR方法MethyLight分析了91个肺癌细胞系中23个位点的甲基化状态。基因PTGS2（COX2）、CALCA、MTHFR、ESR1、MGMT、MYOD1和APC在小细胞肺癌（SCLC）和非小细胞肺癌细胞系（NSCLC）之间的CpG岛甲基化水平上显示出统计学上的显著差异。使用由这七个位点组成的一组进行层次聚类产生了两个主要组，其中一组包含78%的SCLC系。在该组中，一个大的聚类几乎完全由SCLC细胞系组成。我们的结果表明，NSCLC和SCLC细胞系之间的DNA甲基化模式不同，并表明这些模式可发展成为一种强大的分子标记，以实现肺癌的准确诊断。
