Park Jong, Brena Romulo Martin, Gruidl Mike, Zhou Jun, Huang Tim, Plass Christoph, Tockman Melvyn S
Division of Cancer Prevention and Controls, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia drive, Tampa, FL 33612, USA.
Cancer Biomark. 2005;1(2-3):193-200. doi: 10.3233/cbm-2005-12-307.
Lung cancer remains the leading cause of cancer related mortality, accounting for almost one-third of cancer deaths in men and one-fourth of cancer deaths in women; 160,440 lung cancer deaths are expected in 2004. Survival from lung cancer depends mainly upon the stage at presentation. As localized tumors generally do not cause symptoms, the disease is usually diagnosed in symptomatic patients at advanced stages when the prognosis is poor. As a result, the overall 5-year lung cancer survival rate is only 15%. It is well known that epigenetic alterations such as DNA methylation of CpG dinucleotides located in CpG islands within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could identify potential biomarkers for lung cancer risk. Our goal for this study is to identify novel hypermethylated genes in lung cancer. We have investigated the methylation profiles of DNA samples from 14 paired lung tumor and adjacent normal tissues resected from the same individuals using restriction landmark genomic scanning (RLGS). We could assess the DNA methylation status of an average of 2,012 CpG islands for each tumor. We identified 162 differentially methylated loci where CpG islands were hypermethylated in lung tumors but not in adjacent non-cancer tissues. Among 162 sites of differential DNA methylation, detected from at least one tumor/normal pair, 21 hypermethylated genes were identified that were not reported previously as hypermethylated in lung tumor tissue.
肺癌仍然是癌症相关死亡的主要原因，占男性癌症死亡人数的近三分之一，女性癌症死亡人数的四分之一；预计2004年有160,440人死于肺癌。肺癌的生存率主要取决于确诊时的阶段。由于局部肿瘤通常不会引起症状，该疾病通常在预后较差的晚期有症状的患者中被诊断出来。因此，肺癌的总体5年生存率仅为15%。众所周知，基因调控（启动子）区域内位于CpG岛的CpG二核苷酸的DNA甲基化等表观遗传改变与癌症中的转录沉默有关。关键通路基因的启动子高甲基化可以识别肺癌风险的潜在生物标志物。本研究的目标是在肺癌中鉴定新的高甲基化基因。我们使用限制性地标基因组扫描（RLGS）研究了从同一患者切除的14对肺肿瘤和相邻正常组织的DNA样本的甲基化谱。我们可以评估每个肿瘤平均2,012个CpG岛的DNA甲基化状态。我们鉴定出162个差异甲基化位点，其中CpG岛在肺肿瘤中高甲基化，但在相邻的非癌组织中未高甲基化。在从至少一对肿瘤/正常组织中检测到的162个DNA差异甲基化位点中，鉴定出21个以前未报道在肺肿瘤组织中高甲基化的基因。
