Li Jian, Feng Yun, Tan Yuan, Duan Qianqian, Zhang Qin
Department of Thoracic Surgery, Shanxi Provincial People's Hospital, Shanxi, China.
The Medical Department, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China.
Front Oncol. 2022 Apr 4;12:863560. doi: 10.3389/fonc.2022.863560. eCollection 2022.
A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). Several MET exon 14 skipping alterations have been identified, but different MET exon splice variants tend to have different clinical outcomes which deserve concern. Herein, based on NGS panel analysis, we firstly described a 61-year-old woman with lung adenocarcinoma who harbored a novel MET exon 14 skipping (c.3004_3028+3del) concurrent MET amplification (copy number: 3.91) and benefited from Savolitinib treatment. Moreover, CytoTest MET/CCP7 FISH Probe (c-MET/CCP7 Ratio:1.41 and mean gene copy number:6) and qPCR which based on ABI 7500 also were performed to confirm these two MET alterations. After 2 months of Savolitinib treatment, the clinical evaluation was a partial response (PR). In summary, our finding not only expanded the spectrum of the MET exon14 variant (METex14). Targeted NGS analysis could improve detection of MET alterations in routine practice.
致癌驱动基因MET中导致外显子14转录缺失的剪接位点突变在3%至4%的非小细胞肺癌(NSCLC)患者中出现。已经鉴定出几种MET外显子14跳跃改变,但不同的MET外显子剪接变体往往具有不同的临床结果,值得关注。在此,基于二代测序(NGS) panel分析,我们首次描述了一名61岁的肺腺癌女性患者,其携带一种新的MET外显子14跳跃突变(c.3004_3028+3del),同时伴有MET扩增(拷贝数:3.91),并从赛沃替尼治疗中获益。此外,还进行了CytoTest MET/CCP7荧光原位杂交(FISH)探针检测(c-MET/CCP7比值:1.41,平均基因拷贝数:6)以及基于ABI 7500的定量聚合酶链反应(qPCR),以确认这两种MET改变。赛沃替尼治疗2个月后,临床评估为部分缓解(PR)。总之,我们的发现不仅扩展了MET外显子14变体(METex14)的谱。靶向NGS分析可改善常规实践中MET改变的检测。