Genome-wide unmasking of epigenetically silenced genes in lung adenocarcinoma from smokers and never smokers
Genome-wide unmasking of epigenetically silenced genes in lung adenocarcinoma from smokers and never smokers
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DOI：
10.1093/carcin/bgt494
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发表时间：
2014-06-01
期刊：
影响因子：
4.7
通讯作者：
Belinsky, Steven A.
中科院分区：
文献类型：
--
作者：
Tessema, Mathewos;Yingling, Christin M.;Belinsky, Steven A.
从不吸烟的肺癌(NS)与吸烟者的肺癌在人口学、临床病理和分子水平上显示出显著的区别(S)。对肺癌中特定的遗传和表观遗传改变的研究发现，一些异常的频率和特征因吸烟状况而显著不同。本研究比较了赋形剂(对照组)、组蛋白去乙酰化抑制剂(曲古菌素A)和DNA甲基化抑制剂(5-氮-2‘-脱氧胞苷)对S(n=3)和NS(n=3)肺腺癌细胞系转录组的影响。在经5-氮-2‘-脱氧胞苷处理但不经曲古菌素A处理的两个或多个细胞系(包括仅S组的32个基因和仅NS组的12个基因)重新表达的122个基因中，有80%的基因甲基化有效(98/122)。在对20个正常组织样本和另外14个非小细胞肺癌细胞系(总共20个)进行甲基化分析后，39个基因在正常组织中频繁甲基化(>；20%，4/20)，21个基因在非小细胞肺癌中很少甲基化(
Lung cancer in never smokers (NS) shows striking demographic, clinicopathological and molecular distinctions from the disease in smokers (S). Studies on selected genetic and epigenetic alterations in lung cancer identified that the frequency and profile of some abnormalities significantly differ by smoking status. This study compared the transcriptome of lung adenocarcinoma cell lines derived from S (n = 3) and NS (n = 3) each treated with vehicle (control), histone deacetylation inhibitor (trichostatin A) or DNA methylation inhibitor (5-aza-2'-deoxycytidine). Among 122 genes reexpressed following 5-aza-2'-deoxycytidine but not trichostatin A treatment in two or more cell lines (including 32 genes in S-only and 12 NS-only), methylation was validated for 80% (98/122 genes). After methylation analysis of 20 normal tissue samples and 14 additional non-small cell lung cancer cell lines (total 20), 39 genes frequently methylated in normal (>20%, 4/20) and 21 genes rarely methylated in non-small cell lung cancer (