DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type.

DNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic type.
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DOI:
10.1016/j.lungcan.2009.11.002
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发表时间:
2010-08
期刊:
影响因子:
5.3
通讯作者:
Vesselle, Hubert
Vesselle, Hubert
中科院分区:
医学2区
文献类型:
--
作者:
Hawes, Stephen E.;Stern, Joshua E.;Feng, Qinghua;Wiens, Linda W.;Rasey, Janet S.;Lu, Hiep;Kiviat, Nancy B.;Vesselle, Hubert

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与非小细胞肺癌(NSCLC)患者的非癌肺组织相比,我们以前发现的一些基因在肿瘤中的甲基化频率明显更高。检测非小细胞肺癌中基因的甲基化特征可以洞察恶性转化的不同途径,并为更好地治疗非小细胞肺癌患者提供策略。我们用定量甲基化分析方法检测了117例临床特征良好的非小细胞肺癌患者肺肿瘤标本中27个基因的DNA甲基化状态。在117例非小细胞肺癌中,有10 6例(91%)检测到其中一种以上基因的高甲基化,79%的非小细胞肺癌检测到高水平(甲基化参考百分率≥为4%)。腺癌中APC、CCND2、KCNH5和RUNX基因甲基化的发生率显著高于鳞癌,而CDKN2A基因甲基化在鳞癌中更为常见。KCNH5、KCNH8和RARB基因高甲基化在女性中比男性更常见。APC和CCND2的高甲基化与Ki-67的增殖评分呈负相关。我们发现腺癌或鳞癌患者的肿瘤组织中基因高甲基化频率与男性相比存在差异,这表明有必要进行进一步的研究,以更充分地了解与组织类型和性别相关的NSCLC的潜在不同途径和/或危险因素。
We previously identified a number of genes which were methylated significantly more frequently in the tumor compared to the non-cancerous lung tissues from non-small cell lung cancer (NSCLC) patients. Detection of methylation profiles of genes in NSCLC could provide insight into differential pathways to malignancy and lead to strategies for better treatment of individuals with NSCLC. We determined the DNA methylation status of 27 genes using quantitative MethyLight assays in lung tumor samples from 117 clinically well-characterized NSCLC patients. Hypermethylation was detected in one of more of the genes in 106 (91%) of 117 cases and was detected at high levels (Percentage of Methylation Reference (PMR)≥4%) in 79% of NSCLC cases. Methylation of APC, CCND2, KCNH5 and, RUNX was significantly more frequent in adenocarcinomas compared to squamous cell carcinomas (SCC), while methylation of CDKN2A was more common in SCC. Hypermethylation of KCNH5, KCNH8, and RARB was more frequent in females compared to males. Hypermethylation of APC and CCND2 was inversely associated with proliferation score assessed by Ki-67 level. Our findings of differential gene hypermethylation frequencies in tumor tissues from patients with adenocarcinoma or squamous cell cancers and in females compared to males suggests that further investigation is warranted in order to more fully understand the potential disparate pathways and/or risk factors for NSCLC associated with histologic type and gender.
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