Department of Cardiovascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Cancer Research Institute, Central South University, Changsha, China.
Thorac Cancer. 2018 Apr;9(4):445-451. doi: 10.1111/1759-7714.12603. Epub 2018 Feb 23.
To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China.
RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR. ALK and ROS1 expression levels were tested by Western blot and EGFR mutation using Sanger sequencing.
The RET-positive rate was 2.5% (16/631). RET-positive expression was related to poorer tumor differentiation (P < 0.05). In the 16 RET-positive samples, only two samples of moderately and poorly differentiated lung adenocarcinomas displayed RET rearrangement, both in RET-KIF5B fusion partners. Neither ALK nor ROS1 translocation was found. The EGFR mutation rate in RET-positive samples was significantly lower than in RET-negative samples (P < 0.05).
RET-positive expression in early and mid stage NSCLC cases from south central China is relatively low and is related to poorer tumor differentiation. RET gene alterations (copy number gain and rearrangement) exist in all RET-positive samples. RET-positive expression is a relatively independent factor in NSCLC patients, which indicates that the RET gene may be a novel target site for personalized treatment of NSCLC.
为了确定 RET 是否是 NSCLC 治疗的潜在靶点，我们检测了来自中国中南部的 631 例早期和中期 NSCLC 病例中 RET 基因的状态。
通过 Western blot 鉴定 RET 表达。通过免疫组织化学验证 RET 阳性表达样本。通过 DNA Sanger 测序、TaqMan 拷贝数测定和逆转录-PCR 分析 RET 基因突变、拷贝数变化和重排。通过 Western blot 检测 ALK 和 ROS1 表达水平，并通过 Sanger 测序检测 EGFR 突变。
RET 阳性率为 2.5%（16/631）。RET 阳性表达与肿瘤分化较差相关（P<0.05）。在 16 例 RET 阳性样本中，仅 2 例中低分化肺腺癌显示 RET 重排，均为 RET-KIF5B 融合伙伴。未发现 ALK 或 ROS1 易位。RET 阳性样本的 EGFR 突变率明显低于 RET 阴性样本（P<0.05）。
来自中国中南部的早期和中期 NSCLC 病例中 RET 阳性表达相对较低，与肿瘤分化较差有关。所有 RET 阳性样本均存在 RET 基因改变（拷贝数增加和重排）。RET 阳性表达是 NSCLC 患者的一个相对独立的因素，表明 RET 基因可能是 NSCLC 个体化治疗的新靶点。
