MET gene alterations predict poor survival following chemotherapy in patients with advanced cancer

• Main Authors: Jihoon Ko (Author), Jaeyun Jung (Author), Seung Tae Kim (Author), Jung Yong Hong (Author), Sehhoon Park (Author), Joon Oh Park (Author), Young Suk Park (Author), Ho Yeong Lim (Author), Soomin Ahn (Author), Kyoung-Mee Kim (Author), Won Ki Kang (Author), Jeeyun Lee (Author)
• Format: Book
• Published: Frontiers Media S.A., 2022-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1532-2807; 10.3389/pore.2022.1610697
• Keywords: next-generation sequencing; oncogene; overall survival analysis; MET; MET alterations; chemotherapy; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282; Pathology; RB1-214
• Source: Pathology and Oncology Research, Vol 28 (2022)

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.