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局部晚期非小细胞肺癌患者群体中多个治疗反应相关基因的突变与表达

Mutation and expression of multiple treatment response-related genes in a population with locally advanced non-small cell lung cancer.

作者信息

Lu Hong-Yang, Su Dan, Pan Xiao-Dan, Jiang Hong, Ma Sheng-Lin

机构信息

Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang Cancer Hospital, Hangzhou 310022.

出版信息

Oncol Lett. 2012 Feb;3(2):415-420. doi: 10.3892/ol.2011.502. Epub 2011 Nov 30.

Abstract

Individual therapy based on various pathohistological types and biological characteristics may be the practical trend of advanced non-small cell lung cancer (NSCLC) treatment. To provide a molecular criterion for drug selection, we investigated the incidence of somatic mutation and mRNA expression levels of common genes relevant to treatment response in a population with locally advanced NSCLC. Mutant-enriched and branched DNA-liquidchip technology (bDNA-LCT) were used to detect the somatic mutations in the epidermal growth factor receptor (EGFR), KRAS, BRAF and phosphatidylinositol-3-kinase catalytic α (PIK3CA) genes, and mRNA levels of EGFR, ERCC1, class III β-tubulin (TUBB3) and TYMS, separately, in paraffin tissue blocks from 30 patients with stage IIIA NSCLC. Our current findings revealed that 6, 4 and 2 out of 30 samples were found with mutations in exons 19, 21 and 20 of the EGFR gene, respectively. The mutation incidence of exons 19 and 21 had a positive correlation with EGFR mRNA expression. Mutations in exons 12 and 13 of the K-ras gene were found in 2 out of 30, and 1 out of 30 samples, separately. Three out of 30 samples were found with mutations in codon 542 of the PIK3CA gene. No mutations were found in the BRAF gene. The expression levels of ERCC1 and TUBB3 mRNAs were higher in patients with adenocarcinoma than those in patients with squamous cell carcinoma. The expression of TYMS mRNA in patients with adenocarcinoma was lower than that in patients with squamous cell carcinoma. In conclusion, mutations and mRNA expression of these commonly studied genes provides a basis for the selection of suitable molecular markers for individual treatment in a population with locally advanced NSCLC.

摘要

基于不同病理组织学类型和生物学特征的个体化治疗可能是晚期非小细胞肺癌(NSCLC)治疗的实际趋势。为了提供药物选择的分子标准,我们调查了局部晚期NSCLC患者群体中与治疗反应相关的常见基因的体细胞突变发生率和mRNA表达水平。采用突变富集和分支DNA液相芯片技术(bDNA-LCT)分别检测30例IIIA期NSCLC患者石蜡组织块中表皮生长因子受体(EGFR)、KRAS、BRAF和磷脂酰肌醇-3-激酶催化亚基α(PIK3CA)基因的体细胞突变,以及EGFR、ERCC1、III类β-微管蛋白(TUBB3)和TYMS的mRNA水平。我们目前的研究结果显示,30个样本中分别有6个、4个和2个在EGFR基因的19、21和20外显子中发现突变。19和21外显子的突变发生率与EGFR mRNA表达呈正相关。K-ras基因的12和13外显子突变分别在30个样本中有2个和1个被发现。30个样本中有3个在PIK3CA基因的542密码子中发现突变。BRAF基因未发现突变。腺癌患者的ERCC1和TUBB3 mRNA表达水平高于鳞状细胞癌患者。腺癌患者的TYMS mRNA表达低于鳞状细胞癌患者。总之,这些常用研究基因的突变和mRNA表达为局部晚期NSCLC患者群体的个体化治疗选择合适的分子标志物提供了依据。

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