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首页> 美国卫生研究院文献>Molecular Oncology >Genome‐wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR KRAS and TP53 mutation status gene expression and prognosis
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Genome‐wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR KRAS and TP53 mutation status gene expression and prognosis

机译：肺腺癌的全基因组DNA甲基化分析：与EGFRKRAS和TP53突变状态基因表达和预后的关系

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Background: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. Results: We determined whole‐genome DNA methylation profiles of 164 fresh frozen lung adenocarcinoma samples and 19 samples of matched normal lung tissue using the Illumina Infinium 450K array. A large number of differentially methylated CpGs in lung adenocarcinoma tissue were identified, and specific methylation profiles were observed in tumors with mutations in the EGFR‐, KRAS‐ or TP53 genes and according to the patients' smoking status. The methylation levels were correlated with gene expression and both positive and negative correlations were seen. Methylation profiles of the tumor samples identified subtypes of tumors with distinct prognosis, including one subtype enriched for TP53 mutant tumors. A prognostic index based on the methylation levels of 33 CpGs was established, and was significantly associated with prognosis in the univariate analysis using an independent cohort of lung adenocarcinoma patients from The Cancer Genome Atlas project. CpGs in the HOX B and HOX C gene clusters were represented in the prognostic signature. Conclusions: Methylation differences mirror biologically important features in the etiology of lung adenocarcinomas and influence prognosis.
机译：背景：DNA甲基化改变是肿瘤发生中的早期事件，对调节癌细胞中的基因表达很重要。肺癌患者的预后通常较差，需要更深入地了解肺腺癌肿瘤的表观遗传学及其预后意义。结果：我们使用Illumina Infinium 450K阵列确定了164个新鲜的冷冻肺腺癌样品和19个匹配的正常肺组织样品的全基因组DNA甲基化谱。在肺腺癌组织中鉴定出大量差异甲基化的CpGs，并且根据患者的吸烟状况，在EGFR，KRAS或TP53基因突变的肿瘤中观察到了特定的甲基化谱。甲基化水平与基因表达相关，并且看到正相关和负相关。肿瘤样品的甲基化谱鉴定出具有不同预后的肿瘤亚型，包括一种富含TP53突变体肿瘤的亚型。建立了基于33个CpGs甲基化水平的预后指标，并且使用来自癌症基因组图谱项目的独立队列的肺腺癌患者的单变量分析，该预后与单因素分析的预后显着相关。 HOX B和HOX C基因簇中的CpGs代表了预后。结论：甲基化差异反映了肺腺癌的病因学及其影响预后的生物学重要特征。

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