中山市非小细胞肺癌患者EGFR基因与EML4-ALK融合基因突变的统计分析

Statistical analysis of EGFR mutation and EML4-ALK gene fusion in non-small cell lung cancer patients of Zhongshan City

目的检测广东省中山市非小细胞肺(NSCLC)癌患者表皮生长因子受体(EGFR)基因和棘皮动物微管相关蛋白样-4与渐变性淋巴瘤激酶(EML4-ALK)融合基因的突变情况,及与NSCLC临床病理特征的关系。方法通过探针扩增阻滞突变系统(ARMS)荧光定量PCR法对到中山市人民医院就诊的753例NSCLC患者进行EGFR基因及EML4-ALK融合基因检测,研究其突变率及与临床特征的相关性,探讨NSCLC患者EGFR基因和EML4-ALK融合基因突变的意义。结果 753例NSCLC患者中EGFR基因突变率43.16%(325/753),其中19和21号外显子突变率最高,分别为43.08%(140/325)和47.38%(154/325),21号外显子主要是L858R突变。EGFR突变率高的NSCLC患者以女性、无吸烟史、腺癌、腺鳞癌、腺癌转移者多见(P<0.05),与患者年龄无相关性(P>0.05)。对EGFR基因检测中的110例病例同时进行了EML4-ALK融合基因检测,突变率为9.09%(10/110),突变体1型的突变率(80%)明显高于突变体2、3型(各10%),EML4-ALK基因突变患者多为年龄偏小者(P<0.05),与性别、吸烟史及病理分型差异均无统计学意义(P>0.05)。并检测到1例EGFR和EML4-ALK共存突变的患者。结论中山市NSCLC患者的EGFR突变率与国内外文献报道的结果基本一致,因此,EGFR基因及EML4-ALK融合基因检测是分子靶向治疗NSCLC患者的重要依据和必要检测手段。

Objective To detect the mutation of epidermal growth factor receptor（EGFR）gene,fusion of echinoderms microtubule associated protein sample-4and gradual change of lymphoma kinase（EML4-ALK）gene,as well as describe their relationship with the clinicopathological features in patients with non-small cell lung cancer（NSCLC）from Zhongshan city of Guangdong province.Methods Mutations of EGFR gene and EML4-ALK fusion gene in 753 NSCLC patients from Zhongshan People′s hospital were detected by ARMS real-time PCR.To study the relationship between the mutation and clinical features and explore the significance of EGFR gene mutation and EML4-ALK fusion in NSCLC.Results The EGFR mutation rate of 753 NSCLC patients is43.16%（325/753）,with highest mutation rate in 19 and 21exons,43.08%（140/325）and 47.38%（154/325）respectively,and the main mutation in 21 exon is L858 Rmutation.EGFR mutation is more common in female/non-smoking patients,or patients with adenocarcinoma/adenosquqmous carcinoma/adenocarcinoma metastasis（P0.05）,but not relates with the age of patients（P0.05）.The EML4-ALK fusion gene of 110 patients whose EGFR mutation were checked were simultaneously detected,showing a 9.09%（10/110）mutation rate,and the mutation rate in type 1（80%）is significantly higher than type 2（10%）and 3（10%）.Patients with EML4-ALK gene mutation tend to be younger（P0.05）,but the EML4-ALK gene mutation rates show no significant differences in groups classified by gender,smoking history or pathological classification（P0.05）.EGFR gene mutation and EML4-ALK fusion were detected in one patient simultaneously.Conclusion The EGFR mutation rate of patients with NSCLC in Zhongshan city is consistent with results reported in domestic and foreign literatures.Detections of EGFR gene mutation and EML4-ALK fusion are necessary test items,providing important evidence in molecular targeting therapy in NSCLS.