Increasing evidence points to the presence of low-level de novo T790M mutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations. T790M was detected in 42 of 109 pre-treatment samples (38.5%). Median variant allele frequency was 0.14% (range 0.02–28.5%). Overall response rate to first generation EGFR tyrosine kinase inhibitors (TKI) was 67% regardless of T790M status. The median progression free survival was 10.7 (IQR 5.6–19.9) versus 6.7 (IQR 3.5–20.8) months in T790M negative and positive patients respectively. T790M positivity correlated with increased rate of early disease progression. It also correlated with increased mortality (HR 3.1 95%CI 1.2–8.1, p = 0.022) in patients who did not respond to TKI treatment. We detected a significant rate of low-level pre-treatment T790M mutations in NSCLC using highly sensitive dPCR. Low-level pre-treatment T790M did not impact treatment response rate or overall survival, but was associated with increased rate of early progression on TKI therapy.

越来越多的证据表明，携带活化EGFR突变的非小细胞肺癌（NSCLC）患者存在低水平的从头T790M突变。我们利用数字PCR（dPCR）（一种高度敏感的基因突变检测方法）来检测NSCLC肿瘤样品中的治疗前T790M突变，并将T790M状态与临床特征和患者预后相关联。从治疗前的NSCLC肿瘤组织中提取具有已知活化EGFR的DNA在2010年10月至2017年5月间在PathWest实验室诊断出的突变被用于进行靶向dPCR以定量检测T790M突变。在109个预处理样品中的42个（38.5％）中检测到T790M。中位变异等位基因频率为0.14％（范围为0.02–28.5％）。无论T790M状态如何，对第一代EGFR酪氨酸激酶抑制剂（TKI）的总体缓解率为67％。T790M阴性和阳性患者的中位无进展生存期分别为10.7（IQR 5.6-19.9）和6.7（IQR 3.5-20.8）月。T790M阳性与疾病早期进展率增加相关。它也与对TKI治疗无反应的患者死亡率增加（HR 3.1 95％CI 1.2–8.1，p = 0.022）相关。我们使用高度敏感的dPCR检测到了NSCLC中低水平的预处理T790M突变的发生率。低水平的治疗前T790M不会影响治疗反应率或总体生存率，但与TKI治疗的早期进展率增加相关。