Different MET gene alterations in lung adenocarcinoma patients
Abstract
Introduction. In this study, we attempted to detect selected abnormalities in the MET gene using various molecular techniques.
Material and methods. Twenty-six lung adenocarcinoma patients had a diagnosis of abnormalities in the genes: EGFR, ALK, ROS1, MET, and RET. They were diagnosed using various techniques and assessment of PD-L1 expression using immunohistochemistry. Copy number variation of MET gene was assessed by qPCR and FISH techniques, MET exon 14 mutation by RT-PCR method, and MET mRNA expression by the RT-qPCR technique. Statistical analyses were performed using Statistica v. 13.1 and MedCalc 15.8.
Results. Most patients (57.7%) had a high MET gene copy number in the qPCR method, which was not confirmed by the FISH method. A significant positive correlation (R = +0.573, p = 0.0022) between the MET gene copy number assessed with the qPCR method and the relative MET mRNA expression was found.
Conclusions. The positive correlation between the MET mRNA expression and the MET gene copy number in the qPCR test indicates that these methods could complement each other. The performance of these two tests simultaneously increases the reliability of the MET gene assessment
Keywords: MET geneadenocarcinomalung cancer
References
- Organ SL, Tsao MS. An overview of the c-MET signaling pathway. Ther Adv Med Oncol. 2011; 3(1 Suppl): S7–SS19.
- AACR Project GENIE Consortium. AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov. 2017; 7(8): 818–831.
- Drilon A, Cappuzzo F, Ou SHI, et al. Targeting MET in Lung Cancer: Will Expectations Finally Be MET? J Thorac Oncol. 2017; 12(1): 15–26.
- Paik PK, Felip E, Veillon R, et al. Tepotinib in Non-Small-Cell Lung Cancer with Exon 14 Skipping Mutations. N Engl J Med. 2020; 383(10): 931–943.
- Wolf J, Seto T, Han JY, et al. GEOMETRY mono-1 Investigators. Capmatinib in Exon 14-Mutated or -Amplified Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383(10): 944–957.
- Mok T, Carbone D, Hirsch F. IASLC atlas of EGFR testing in lung cancer. 2017. https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-egfr-testing-lung-cancer-guidebook.
- Tsao MS, Kerr KM, Dacic S et al. The IASLC Atlas of PD-L1 Testing in Lung Cancer. 2017. https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-pd-l1-testing-lung-cancer.
- Tsao MS, Hirsch FR, Yatabe Y. IASLC atlas of ALK and ROS1 testing in lung cancer. 2016. https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-alk-and-ros1-testing-lung-cancer.
- Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 2009; 27(10): 1667–1674.
- de Melo Gagliato D, Jardim DL, Falchook G, et al. Analysis of MET genetic aberrations in patients with breast cancer at MD Anderson Phase I unit. Clin Breast Cancer. 2014; 14(6): 468–474.
- Kerr KM, Dafni U, Schulze K, et al. ETOP Lungscape Consortium, Lungscape Consortium. Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project. Lung Cancer. 2017; 111(1): 143–149.
- Dziadziuszko R, Wynes MW, Singh S, et al. Correlation between MET gene copy number by silver in situ hybridization and protein expression by immunohistochemistry in non-small cell lung cancer. J Thorac Oncol. 2012; 7(2): 340–347.
- Kowalczuk O, Kozlowski M, Niklinska W, et al. Increased MET Gene Copy Number but Not mRNA Level Predicts Postoperative Recurrence in Patients with Non-Small Cell Lung Cancer. Transl Oncol. 2014; 7(5): 605–612.
- Aguado C, Teixido C, Román R, et al. Multiplex RNA-based detection of clinically relevant MET alterations in advanced non-small cell lung cancer. Mol Oncol. 2021; 15(2): 350–363.
- Kim JH, Kim HSu, Kim BJ. Prognostic value of MET copy number gain in non-small-cell lung cancer: an updated meta-analysis. J Cancer. 2018; 9(10): 1836–1845.