AUTHOR=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
TITLE=MET gene alterations predict poor survival following chemotherapy in patients with advanced cancer
JOURNAL=Pathology and Oncology Research
VOLUME=28
YEAR=2022
URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610697
DOI=10.3389/pore.2022.1610697
ISSN=1532-2807
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.