EGFR突变丰度的检测及其临床意义

Detection and Clinical Significance of Abundance of EGFR Mutation

具有表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变的非小细胞肺癌患者对酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)具有良好反应,但是即使存在相同突变,不同患者对TKIs的反应也不一致。推测突变分子含量的不同是TKIs反应不一的部分原因,具有更高EGFR突变"丰度"的肿瘤患者可能从TKIs中获益更多。EGFR突变可根据检测方法敏感性的不同,定量检测突变分子比例以及突变蛋白表达等进行半定量或定量检测。EGFR突变丰度可能有助于反映肿瘤异质性,评估疾病进程,预测TKIs药物敏感性,早期发现耐药,具有重要的临床意义。

Non-small cell lung cancer（NSCLC） patients, with sensitive epidermal growth factor receptor（EGFR） mutations react well to tyrosine kinase inhibitors（TKIs）. However, the efficacy of TKIs on patients with the same mutant types differs dramatically. It is implied that the different quantities of mutant alleles could be one of the reasons underlying. Patients with high abundance of EGFR mutation might benefit more from TKIs. There are no universal standards for the definition of EGFR mutant abundance. Abundance could be semi-quantified according to the different sensitivities of detection methods, quantified with quantifying detection techniques such as digital PCR or next generation sequencing, or quantified based on the expression of mutant proteins. The different abundances of primary and metastatic diseases could reflect the heterogeneity of the tumors. The pre-treatment level or the dynamic change of EGFR mutant abundance could help observe the course of the diseases and predict the efficacy of TKIs. TKIs resistance could be detected by change of abundance prior to image manifestations. Besides, the abundance of T790 M could also predict drug efficacy and resistance of the first and third generation TKIs. Thus the detection of EGFR mutant abundance has important clinical significance. The standardization and correction of abundance needs more exploration.