背景:为了帮助肿瘤药物开发,我们调查了在临床实践中接受下一代测序(NGS)的2,239例肿瘤患者的MET原癌基因受体酪氨酸激酶基因异常.材料和方法:从2019年11月到2021年1月,访问肿瘤诊所的2,239名晚期实体瘤患者接受了NGS。NGS面板包括使用档案组织样本的>500个综合NGS测试。1,137(50.8%)和1,761(78.7%)患者可获得程序性死亡配体1(PD-L1)22C3测定结果和关于初始化疗的临床记录,分别进行总生存期(OS)分析。结果:2,239例患者代表37种癌症。NGS小组包括>500个基因,微卫星不稳定状态,肿瘤突变负担,和融合。最常见的癌症类型是结直肠癌(N=702),胃(N=481),和肉瘤(N=180)。在212例患者中检测到MET像差。所有MET扩增的肿瘤都有微卫星稳定状态,和8具有较高的肿瘤突变负担。在46例MET扩增癌症患者中,8例免疫组织化学显示MET阳性蛋白表达(2+和3+)。在10例患者中检测到MET融合。MET融合的伙伴基因包括ST7、TFEC、LRRD1,CFTR,CAV1、PCM1、HLA-DRB1和CAPZA2。在生存分析中,MET基因融合扩增患者的OS和无进展生存期(PFS)比无MET基因融合扩增患者短.因此,MET畸变被确定为化疗反应的一个因素。结论:大约2.1%和0.4%的晚期实体瘤患者出现MET基因扩增和融合,分别,与没有MET基因扩增或融合的患者相比,对化疗的反应更差,OS和PFS明显更短。
Background: To aid in oncology drug development, we investigated MET proto-oncogene receptor tyrosine kinase gene aberrations in 2,239 oncology patients who underwent next-generation sequencing (NGS) in clinical practice. Materials and methods: From November 2019 to January 2021, 2,239 patientswith advanced solid tumors who visited oncology clinics underwent NGS. The NGS panel included >500 comprehensive NGS tests using archival tissue specimens. Programmed death-ligand 1(PD-L1) 22C3 assay results and clinical records regarding initial chemotherapy were available for 1,137 (50.8%) and 1,761 (78.7%) patients, respectively for overall survival (OS) analysis. Results: The 2,239 patients represented 37 types of cancer. The NGS panel included >500 genes, microsatellite instability status, tumor mutational burden, and fusions. The most common cancer types were colorectal (N = 702), gastric (N = 481), and sarcoma (N = 180). MET aberrations were detected in 212 patients. All MET-amplified tumors had microsatellite stable status, and 8 had a high tumor mutational burden. Of 46 patients with MET-amplified cancers, 8 had MET-positive protein expression by immunohistochemistry (2+ and 3+). MET fusion was detected in 10 patients. Partner genes of MET fusion included ST7, TFEC, LRRD1, CFTR, CAV1, PCM1, HLA-DRB1, and CAPZA2. In survival analysis, patients with amplification of MET gene fusion had shorter OS and progression-free survival (PFS) than those without. Thus, MET aberration was determined to be a factor of response to chemotherapy. Conclusion: Approximately 2.1% and 0.4% of patients with advanced solid tumors demonstrated MET gene amplification and fusion, respectively, and displayed a worse response to chemotherapy and significantly shorter OS and PFS than those without MET gene amplification or fusion.