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EPIDEMIOLOGICAL AND MOLECULAR ASPECTS OF MET GENE MUTATIONS IN LUNG CANCER
Mehdizadeh S.Q., Vekilov V.N.


DOI: 10.61775/2413-3302.v2i40.03


SUMMARY
As molecular profiling and targeted therapies expand in non-small cell lung cancer (NSCLC), MET alterations have gained increasing clinical relevance; however, uncertainties regarding their prognostic implications continue to make this topic highly pertinent. Objective. To perform a comprehensive analysis of the clinical and demographic characteristics of patients with NSCLC harboring MET gene mutations, and to evaluate the potential association of these mutations with tumor aggressiveness and risk factors, including smoking. Materials and Methods. This retrospective study included 187 patients who underwent molecular analysis of FFPE samples using real-time PCR between 2014 and 2024. MET mutations were identified in 16 patients. Patients were stratified by age, sex, histological grade, and smoking status, and statistical analyses were performed. Results and Discussion. The majority of patients with MET mutations were over 65 years old, with a predominance of males. High histological grade (G3–G4) was observed in 81.25% of cases. While 56.25% of patients had a history of smoking, ROC analysis did not show a statistically significant association between tobacco use and tumor aggressiveness. These findings highlight the complex clinical impact of MET mutations and the need for further investigation. Conclusion. The study emphasizes the importance of molecular diagnostics and personalized therapy. Further research is recommended to clarify the prognostic and therapeutic role of MET mutations.
Keywords: MET mutation, lung cancer, molecular diagnostics, personalized therapy


REFERENCES
  1. Awad M.M., Oxnard G.R., Jackman D.M., et al. MET exon 14 mutations in NSCLC // J Clin Oncol. - 2016; 34(7):721–730; https://doi.org/10.1200/JCO.2015.63.8922
  2. Drilon A., Cappuzzo F., Ou S.I., Camidge D.R., et al. Targeting MET in lung cancer // Clin Cancer Res. - 2017; 23(12):2899–2905; https://doi.org/10.1158/1078-0432.CCR-16-2279
  3. Tong J.H., Yeung S.T., Chan A.S., et al. MET overexpression and gene amplification in NSCLC // Lung Cancer. - 2016; 94:1–6; https://doi.org/10.1016/j.lungcan.2016.03.011
  4. Liu X., Xie F., Li Q., et al. Molecular analysis of MET-mutated lung cancer // Oncotarget. - 2017; 8(61):104727–104734; https://doi.org/10.18632/oncotarget.22035
  5. Reungwetwattana T., Liang Y., Zhu V., Ou S.I. MET alterations in lung cancer // Curr Treat Options Oncol. - 2018; 19(3):10; https://doi.org/10.1007/s11864-018-0536-x
  6. Camidge D.R., Ou S.I., Sholl L.M., et al. MET alterations in lung cancer: predictive or prognostic? // Lancet Oncol. - 2022; 23(3):e125–e136; https://doi.org/10.1016/S1470-2045(21)00511-6
  7. Fujino T., Suda K., Kim Y.H., et al. MET exon 14 mutation and immunotherapy // J Thorac Oncol. - 2021; 16(3):418–430; https://doi.org/10.1016/j.jtho.2020.11.027
  8. Reichel J., Klingbiel D., Kocher F., et al. Frequency and clinical relevance of MET mutations // Mod Pathol. - 2018; 31(1):38–50; https://doi.org/10.1038/modpathol.2017.106
  9. Sakai K., Takeuchi K., Nakanishi Y., et al. MET mutations and therapy response // Cancer Sci. - 2020; 111(9):3358–3366; https://doi.org/10.1111/cas.14501
  10. Lim S.M., Kim H.R., Lee J.S., et al. MET mutation: diagnosis and targeted therapy // Cancer Res Treat. - 2019; 51(2):613–623; https://doi.org/10.4143/crt.2018.478
  11. Mehdizadeh S.G. A retrospective molecular epidemiological analysis of EML4 ALK gene fusions in non-small cell lung cancer patients in the Azerbaijani population (2014–2024) // Egypt J Med Hum Genet. - 2025, 26, 180; https://doi.org/10.1186/s43042-025-00808-2
  12. Zhang Y., Kim H., Lee J., et al. MET exon 14 skipping mutation in NSCLC and response to MET inhibitors // J Thorac Oncol. - 2021; 16(3):429–437; https://doi.org/10.1016/j.jtho.2020.11.028
  13. Hong D.S., Fakih M., Strickler J.H., et al. Targeting MET dysregulation in cancer // Cancer Discov. - 2021; 11(2):489–505; https://doi.org/10.1158/2159-8290.CD-20-1484
  14. Gendreau S., Shaw A.T., Liu G., et al. MET inhibitors in NSCLC: clinical development and resistance mechanisms // J Clin Med. - 2020; 9(5):1320; https://doi.org/10.3390/jcm9051320
  15. The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma // Nature. - 2014; 511:543–550; https://doi.org/10.1038/nature13385
  16. Frampton G.M., Fichtenholtz A., Otto G., et al. Genomic profiling in lung cancer // Nat Commun. - 2015; 6:8651; https://doi.org/10.1038/ncomms9651
  17. Lee G.D., Kim Y., Park J., et al. Clinicopathologic features of MET-mutant lung cancer // Pathol Res Pract. - 2020; 216(1):152758; https://doi.org/10.1016/j.prp.2019.152758