肺腺癌中表皮生长因子受体基因突变与拷贝数的检测分析

目的检测肺腺癌组织中表皮生长因子受体（EGFR）19、21外显子基因突变和拷贝数，分析EGFR基因突变和拷贝数变化的相关性。方法应用荧光定量PCR技术和荧光原位杂交（FISH）技术分别检测58例肺腺癌患者肿瘤组织中的EGFR基因突变和基因扩增，用X^2检验进行数据分析。结果58例肺腺癌患者组织中，EGFR19、21外显子突变率为43．1％（25／58），其中2例存在两种类型的突变。EGFR基因拷贝数增加阳性率为51．7％（30／58），包括8例扩增，22例高多体扩增。不同分化程度的肺腺癌组织间，扩增阳性率差异无统计学意义（P〉0．05），低分化癌的突变率低于高、中分化癌（P〈O．05）。EGFR基因突变与EGFR基因拷贝数之间显著相关（P〈0．01）。结论肺腺癌组织具有较高的EGFR基因突变率和扩增阳性率；联合检测EGFR基因拷贝数和基因突变，更有利于靶向药物的筛选。

Analysis on the relationship of epidermal growth factor receptor gene mutation with gene copy number in lung adenocarcinoma

Objective To detect epidermal growth factor receptor (EGFR) 19, 21 exon gene mutation and gene copy number in lung adenocarcinoma tissue, and to analyze the relationship of EGFR 19, 21 mutation with copies number. Methods EGFR mutations and gene copy number in the tissue samples embedded by paraffin and fixed by for marlin from 58 cases of lung adenocarcinoma were detected by RT-PCR and FISH. The statistical data were analyzed by chi-square test.Results Of 58 cases, the overall single mutation rate of EGFR exon 19, 21 was 43.1% (25/58), and 2 cases contained both types of the mutation.The overall FISH positive rate of EGFR was 51.7 % (30/58), including 8 positive amplification and 22 highly ploidy amplification. The testing results showed that there had no statistically differences in FISH positive rates of EGFR mutation among different differentiation lung adenocarcinoma tissues(P ＞0.05), and the FISH positive rates of EGFR mutation in poorly differentiated cancer were lower than those in moderatedly differentiated and well-differentiated cancer (P ＜0.05). EGFR mutation was closely related to EGFR gene copies (P ＜0.01). Conclusion There are high EGFR mutation frequencies and FISH positive rates in lung adenocarcinoma tissue; Combined detection of EGFR mutation and gene copy number may provide a better approach in selecting patients who may benefit from anti-EGFR target therapy.