人类T（短尾同源物）基因在非小细胞肺癌中的表观遗传沉默
Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer.
作者信息
Park Jong Chul, Chae Young Kwang, Son Choon Hee, Kim Myoung Sook, Lee Juna, Ostrow Kimberly, Sidransky David, Hoque Mohammad Obaidul, Moon Chulso
机构信息
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, 1550 Orleans Street, Baltimore, MD 21231, USA.
出版信息
Biochem Biophys Res Commun. 2008 Jan 11;365(2):221-6. doi: 10.1016/j.bbrc.2007.10.144. Epub 2007 Oct 31.
Early detection of lung cancer is challenging due to a lack of adequate biomarkers. To discover novel tumor suppressor genes (TSGs) silenced by aberrant promoter methylation, we analyzed the gene expression profiles of two lung adenocarcinoma cell lines using pharmacologic-unmasking and subsequent microarray-analysis. Among 617 genes upregulated, we selected 30 genes and investigated the methylation status of their promoters by bisulfite sequencing analysis. Aberrant methylation was detected in four genes (CRABP2, NOEY2, T, MAP2K3) in at least one lung adenocarcinoma cell lines. Furthermore, the T promoter was methylated in 60% of primary lung adenocarcinomas versus 13% of non-malignant lung tissues. Conversely, RT-PCR analysis revealed T expression was low in lung tumors, while high in normal tissues. In addition, no non-synonymous mutations related to gene silencing were found. While further analysis is warranted, our results suggest that T has the potential to be a novel candidate TSG in lung cancer.
由于缺乏足够的生物标志物，肺癌的早期检测具有挑战性。为了发现因异常启动子甲基化而沉默的新型肿瘤抑制基因（TSG），我们使用药物去甲基化和随后的微阵列分析来分析两种肺腺癌细胞系的基因表达谱。在617个上调基因中，我们选择了30个基因，并通过亚硫酸氢盐测序分析研究了它们启动子的甲基化状态。在至少一种肺腺癌细胞系中，在四个基因（CRABP2、NOEY2、T、MAP2K3）中检测到异常甲基化。此外，T启动子在60%的原发性肺腺癌中发生甲基化，而在非恶性肺组织中为13%。相反，RT-PCR分析显示T在肺肿瘤中表达低，而在正常组织中表达高。此外，未发现与基因沉默相关的非同义突变。虽然有必要进行进一步分析，但我们的结果表明T有可能成为肺癌中一种新型的候选TSG。
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