原发性肝癌表皮生长因子受体突变的研究

Analysis of EGFR mutation status in primary hepatocarcinoma patients

目的对原发性肝癌患者EGFR基因进行检测,分析EGFR基因突变与原发性肝癌及患者年龄组成的关系。方法对2 507例确诊原发性肝癌的石蜡包埋组织样本用PCR扩增法和双向测序法检测EGFR基因突变状态。结果 2 507例患者仅检测出620例(24.74%)EGFR基因20外显子同义突变Q787Q(2361G>A)和263例(10.49%)19内含子点突变(2284-60T>C);EGFR基因突变与患者性别、病理类型无关(P>0.05),与患者的年龄段组成明显相关(P<0.05),且基于年龄段的分布,20外显子突变与19内含子突变呈显著正相关(P<0.05)。结论本研究中未发现EGFR基因热点突变。同义突变位点Q787Q尚存在进一步需要被证实的功能。20外显子突变和19内含子突变与患者年龄分布有明显相关性,可为原发性肝癌患者提供更具体的个体化治疗方案。

Objective To detect the EGFR mutations（exon18, 19, 20, 21） in primary hepatocarcinoma（PHC） tissue, and to study the correlation between the EGFR mutations and the ages and clinical features of the patients with the aim of supporting the development of new molecular targeting therapy for PHC patients.Methods Paraffin embedded tissues from 2 507 cases were collected, and EGFR mutations were detected using PCR and bidirectional sequencing. Results Out of the 2 507 cases of PHC, there were 620 PHC patients carrying a silent mutation, which showed a G-to-A transition at nucleotide 2361 in exon 20 of the gene.Furthermore, 263 PHC patients（10.49%） were found to be carrying the mutation 2284-60T〉C in intron 19 The EGFR mutations 2361G〉C and 2284-60 were not related to sex or pathology（P〉0.05）, but were related to the age of the PHC patients（P〈0.05）. In addition, a significant positive correlation was found between the mutation rate of exon 20 and intron 19（P〈0.05） based on the ages of the PHC patients. Conclusion There were no hot mutations found in the EGFR gene. The features of the EGFR 2361G〉C mutation need to be analyzed further. Investigation into the characteristics of exon 20 and intron 19 may provide avenues for more individualized therapy in PHC.