Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC).
Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC).
复制标题
非小细胞肺癌 (NSCLC) 中频繁出现的启动子甲基化和 PIK3CA 扩增
DOI：
10.1186/1471-2407-11-147
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发表时间：
2011-04-20
期刊：
影响因子：
3.8
通讯作者：
Hou P
中科院分区：
文献类型：
--
作者：
Ji M;Guan H;Gao C;Shi B;Hou P
背景
肺癌是全球癌症相关死亡的主要原因。肺癌中常见的遗传和表观遗传改变包括启动子甲基化、基因突变和基因组扩增。然而，遗传和表观遗传事件之间的相互作用及其在肺肿瘤发生中的意义仍然知之甚少。
方法
我们分别使用定量甲基化特异性PCR（Q-MSP）和实时定量PCR测定6个基因的启动子甲基化和PIK 3CA扩增，并在一个临床特征良好的非小细胞肺癌（NSCLC）大队列中探索启动子甲基化与PIK 3CA扩增的相关性。
结果
在NSCLC中观察到高度频繁的启动子甲基化。在100%的诊断特异性下，发现6个基因中的每一个具有极好的灵敏度，范围从45.8%到84.1%。启动子甲基化与组织学类型有关。与腺癌（ADC）相比，CALCA、CDH 1、DAPK 1和EVX 2的甲基化在鳞状细胞癌（SCC）中更常见。相反，ADC中RASSF 1A甲基化的频率高于SCC。此外，PIK 3CA扩增在NSCLC中常见，并且与某些临床病理特征相关，例如吸烟史、组织学类型和胸膜凹陷。重要的是，某些基因的异常启动子甲基化与PIK 3CA扩增显著相关。
结论
我们的数据显示，中国NSCLC人群中存在高频率的启动子甲基化和PIK 3CA扩增，并首次证明了基因甲基化与PIK 3CA扩增的相关性，表明这些表观遗传事件可能是PI 3 K/Akt通路过度激活的结果。
Background
Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood.
Methods
We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC).
Results
Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification.
Conclusions
Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.
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影响因子：
11.2
作者：
Le Calvez, F;Mukeria, A;Hainaut, P
通讯作者：
Hainaut, P
影响因子：
5.3
作者：
Kawano, Osamu;Sasaki, Hidefumi;Fujii, Yoshitaka
通讯作者：
Fujii, Yoshitaka
影响因子：
4.8
作者：
Lu, Rong;Wang, Xia;Fang, Jing-Yuan
通讯作者：
Fang, Jing-Yuan
影响因子：
5.3
作者：
Hawes, Stephen E.;Stern, Joshua E.;Feng, Qinghua;Wiens, Linda W.;Rasey, Janet S.;Lu, Hiep;Kiviat, Nancy B.;Vesselle, Hubert
通讯作者：
Vesselle, Hubert
影响因子：
11.5
作者：
Hou, Peng;Liu, Dingxie;Xing, Mingzhao
通讯作者：
Xing, Mingzhao