MET gene alterations predict poor survival following chemotherapy in patients with advanced canceropen access
- Authors
- Ko, Jihoon; Jung, Jaeyun; Kim, Seung Tae; Hong, Jung Yong; Park, Sehhoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Ahn, Soomin; Kim, Kyoung-Mee; Kang, Won Ki; Lee, Jeeyun
- Issue Date
- Nov-2022
- Publisher
- FRONTIERS MEDIA SA
- Keywords
- next-generation sequencing; oncogene; overall survival analysis; MET; MET alterations; chemotherapy; cancer
- Citation
- PATHOLOGY & ONCOLOGY RESEARCH, v.28
- Journal Title
- PATHOLOGY & ONCOLOGY RESEARCH
- Volume
- 28
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/87282
- DOI
- 10.3389/pore.2022.1610697
- ISSN
- 1219-4956
- Abstract
- 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.
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