Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung.
Hypermethylation of CCND2 May Reflect a Smoking-Induced Precancerous Change in the Lung.
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DOI：
10.1155/2011/950140
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发表时间：
2011
影响因子：
--
通讯作者：
Vesselle H
中科院分区：
文献类型：
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作者：
Salskov A;Hawes SE;Stern JE;Feng Q;Jordan CD;Wiens L;Rasey J;Lu H;Kiviat NB;Vesselle H
目前尚不清楚烟草烟雾是否会诱导 DNA 高甲基化作为致癌作用的早期事件或晚期事件（针对明显的癌症组织）。使用 MethyLight 检测，我们分析了来自 151 名无癌症受试者（121 名曾经吸烟者和 30 名从不吸烟者）的 316 个肺组织样本，以了解先前观察到在非小细胞肺癌中高甲基化的 19 个基因的高甲基化情况。在超过 2% 的无癌症受试者中，只有 APC (39%)、CCND2 (21%)、CDH1 (7%) 和 RARB (4%) 高度甲基化。 CCND2 在曾经吸烟者 (26%) 中的高甲基化频率高于从不吸烟者 (3%)。 CCND2 高甲基化还与年龄增加和上叶样本位置相关。在曾经吸烟者 (41%) 和从不吸烟者 (30%) 中，APC 经常高度甲基化。所有受试者中 BVES、CDH13、CDKN2A (p16)、CDKN2B、DAPK1、IGFBP3、IGSF4、KCNH5、KCNH8、MGMT、OPCML、PCSK6、RASSF1、RUNX 和 TMS1 很少高度甲基化 (<2%)。 CCND2 的高甲基化可能反映了吸烟引起的肺部癌前变化。
It remains unknown whether tobacco smoke induces DNA hypermethylation as an early event in carcinogenesis or as a late event, specific to overt cancer tissue. Using MethyLight assays, we analyzed 316 lung tissue samples from 151 cancer-free subjects (121 ever-smokers and 30 never-smokers) for hypermethylation of 19 genes previously observed to be hypermethylated in nonsmall cell lung cancers. Only APC (39%), CCND2 (21%), CDH1 (7%), and RARB (4%) were hypermethylated in >2% of these cancer-free subjects. CCND2 was hypermethylated more frequently in ever-smokers (26%) than in never-smokers (3%). CCND2 hypermethylation was also associated with increased age and upper lobe sample location. APC was frequently hypermethylated in both ever-smokers (41%) and never-smokers (30%). BVES, CDH13, CDKN2A (p16), CDKN2B, DAPK1, IGFBP3, IGSF4, KCNH5, KCNH8, MGMT, OPCML, PCSK6, RASSF1, RUNX, and TMS1 were rarely hypermethylated (<2%) in all subjects. Hypermethylation of CCND2 may reflect a smoking-induced precancerous change in the lung.