Tatematsu Tsutomu, Okuda Katsuhiro, Suzuki Ayumi, Oda Risa, Sakane Tadashi, Kawano Osamu, Haneda Hiroshi, Moriyama Satoru, Sasaki Hidefumi, Nakanishi Ryoichi
Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
J Thorac Dis. 2017 Aug;9(8):2397-2403. doi: 10.21037/jtd.2017.07.02.
A gatekeeper T790M mutation is thought to cause resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. The detection of a 2nd mutation is important for planning the next therapy when patients acquire resistance to the first line EGFR-TKI.
We used a competitive allele-specific polymerase chain reaction (CAST-PCR) to analyze the incidence and clinical significance of T790M mutations in 153 lung adenocarcinomas with EGFR-activating mutations. To increase the sensitivity and specificity of the detection of T790M mutations, we subjected 20 of the 153 cases to a digital PCR. The genomic DNAs were extracted from frozen, surgically resected tumor tissue specimens.
The CAST-PCR detected T790M mutations in 45 (29.4%) of the 153 cases. The analytical sensitivity in the detection T790M mutations was 0.13-2.65% (average 0.27%, median 0.20%). In contrast, the digital PCR, detected T790M mutations in 8 (40%) out of 20 cases.
Our study shows that the pretreatment incidence of T790M mutation was less than that reported in previous studies. In order to clinically use pretreatment EGFR T790M mutation identification method, we should clarify the adequate methods and tissue preserved status.
守门人T790M突变被认为会导致对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗产生耐药性。当患者对一线EGFR-TKI产生耐药性时，检测第二个突变对于规划下一步治疗很重要。
我们使用竞争性等位基因特异性聚合酶链反应（CAST-PCR）分析153例具有EGFR激活突变的肺腺癌中T790M突变的发生率和临床意义。为了提高T790M突变检测的灵敏度和特异性，我们对153例中的20例进行了数字PCR。基因组DNA从冷冻的手术切除肿瘤组织标本中提取。
CAST-PCR在153例中的45例（29.4%）中检测到T790M突变。检测T790M突变的分析灵敏度为0.13-2.65%（平均0.27%，中位数0.20%）。相比之下，数字PCR在20例中的8例（40%）中检测到T790M突变。
我们的研究表明，T790M突变的预处理发生率低于先前研究报道的发生率。为了在临床上使用预处理EGFR T790M突变鉴定方法，我们应该明确适当的方法和组织保存状态。
