Volume 17, Issue 1 (March-2025 2025)                   Iranian Journal of Blood and Cancer 2025, 17(1): 40-46 | Back to browse issues page


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Salimi B, Mabani M, Seifi S, Rostami P, Dehghanifard A, Khosravi N, et al . EGFR Mutations, ROS1, and ALK Rearrangements in Iranian Non-Small Cell Lung Cancer Patients. Iranian Journal of Blood and Cancer 2025; 17 (1) :40-46
URL: http://ijbc.ir/article-1-1683-en.html
1- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
3- Department of Genetic, Ahar Branch, Islamic Azad University, Ahar, Iran.
4- Department of Biology, East Tehran Islamic azad university,Tehran, Iran.
5- Immunology Department, Pasteur Institue of Iran, Tehran, Iran.
6- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. , adkhosravi@yahoo.com
Abstract:   (587 Views)
Background: Driver mutations, particularly in the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS1 genes, are prevalent in non-small cell lung cancer (NSCLC) and significantly influence patient outcomes. These mutations have become crucial biomarkers for targeted therapy, guiding treatment decisions and improving patient survival. Our study aims to evaluate the prevalence of EGFR mutations, ALK, and ROS1 gene rearrangements in a cohort of Iranian NSCLC patients and to investigate their association with patient characteristics.
Materials and Methods: Tissue samples from patients diagnosed with non-small cell lung cancer (NSCLC) were subjected to molecular analysis. EGFR mutations, ALK, and ROS1 gene rearrangements were assessed. Additionally, the correlation between these genetic alterations and patient demographics, including age and gender, was explored.
Results: Driver mutations or rearrangements were detected in approximately one-third of NSCLC cases. EGFR mutations were the most common, occurring in 22.44% of patients. ALK and ROS1 rearrangements were identified in 8.18% and 2.11% of patients, respectively. The EGFR mutation frequency in patients younger than 36 years was 16%. In contrast, the mutation frequency in older patient cohorts ranged from 11% to 15%. Among EGFR mutations, exon 19 deletions (13.35%) and L858R point mutations (6.81%) were the most prevalent. Notably, exon 19 deletions were more frequent in female patients (27.92%) compared to male patients (9.90%).
Conclusion: EGFR mutations were more prevalent than ALK and ROS1 rearrangements in our cohort. Exon 19 deletions and L858R point mutations were the most common EGFR mutations, with a higher frequency observed in female patients. These mutations are frequently associated with lung adenocarcinoma.
Full-Text [PDF 499 kb]   (311 Downloads)    
: Original Article | Subject: Adults Hematology & Oncology
Received: 2025/01/3 | Accepted: 2025/03/6 | Published: 2025/03/30

References
1. Siegel, R.L., K.D. Miller, and A. Jemal, Cancer statistics, 2018. CA: a cancer journal for clinicians, 2018. 68(1): p. 7-30. [DOI:10.3322/caac.21442]
2. Rothschild, S.I., Targeted therapies in non-small cell lung cancer-beyond EGFR and ALK. Cancers, 2015. 7(2): p. 930-949. [DOI:10.3390/cancers7020816]
3. Lynch, T.J., et al., Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New England Journal of Medicine, 2004. 350(21): p. 2129-2139. [DOI:10.1056/NEJMoa040938]
4. Paez, J.G., et al., EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 2004. 304(5676): p. 1497-1500. [DOI:10.1126/science.1099314]
5. Doval, D., et al., Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung. OncoTargets and therapy, 2015: p. 117-123. [DOI:10.2147/OTT.S74820]
6. Lin, J.J. and A.T. Shaw, Recent advances in targeting ROS1 in lung cancer. Journal of thoracic oncology, 2017. 12(11): p. 1611-1625. [DOI:10.1016/j.jtho.2017.08.002]
7. Shi, Y., et al., A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). Journal of thoracic oncology, 2014. 9(2): p. 154-162. [DOI:10.1097/JTO.0000000000000033]
8. Yu, X., et al., The effect of EGFR‐TKIs on survival in advanced non‐small‐cell lung cancer with EGFR mutations: A real‐world study. Cancer Medicine, 2023. 12(5): p. 5630-5638. [DOI:10.1002/cam4.5413]
9. Howlader, N., et al., The effect of advances in lung-cancer treatment on population mortality. New England Journal of Medicine, 2020. 383(7): p. 640-649. [DOI:10.1056/NEJMoa1916623]
10. Zhou, C., et al., BEYOND: a randomized, double-blind, placebo-controlled, multicenter, phase III study of first-line carboplatin/paclitaxel plus bevacizumab or placebo in Chinese patients with advanced or recurrent nonsquamous non-small-cell lung cancer. Journal of clinical oncology, 2015. 33(19): p. 2197-2204. [DOI:10.1200/JCO.2014.59.4424]
11. Marinelli, D., et al., Non-small-cell lung cancer: how to manage ALK-, ROS1-and NTRK-rearranged disease. Drugs in Context, 2022. 11. [DOI:10.7573/dic.2022-3-1]
12. Araki, T., et al., Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance. Japanese Journal of Clinical Oncology, 2023. 53(7): p. 547-561. [DOI:10.1093/jjco/hyad052]
13. Hsieh, R.-K., et al., Female sex and bronchioloalveolar pathologic subtype predict EGFR mutations in non-small cell lung cancer. Chest, 2005. 128(1): p. 317-321. [DOI:10.1378/chest.128.1.317]
14. Mok, T.S., et al., Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New England Journal of Medicine, 2009. 361(10): p. 947-957. [DOI:10.1056/NEJMoa0810699]
15. Girard, N., et al., Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma. European Respiratory Journal, 2012. 39(2): p. 366-372. [DOI:10.1183/09031936.00010111]
16. Graham, R.P., et al., Worldwide frequency of commonly detected EGFR mutations. Archives of pathology & laboratory medicine, 2018. 142(2): p. 163-167. [DOI:10.5858/arpa.2016-0579-CP]
17. Boch, C., et al., The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study. BMJ open, 2013. 3(4): p. e002560. [DOI:10.1136/bmjopen-2013-002560]
18. Rosell, R., et al., Screening for epidermal growth factor receptor mutations in lung cancer. New England Journal of Medicine, 2009. 361(10): p. 958-967. [DOI:10.1056/NEJMoa0904554]
19. Sahoo, R., et al., Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer, 2011. 73(3): p. 316-319. [DOI:10.1016/j.lungcan.2011.01.004]
20. Jain, D., et al., Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: a preliminary study. Indian Journal of Medical Research, 2016. 143(3): p. 308-314. [DOI:10.4103/0971-5916.182621]
21. Chougule, A., et al., Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity. PloS one, 2013. 8(10): p. e76164. [DOI:10.1371/journal.pone.0076164]
22. Yang, P.-C., et al., Molecular epidemiological prospective study of EGFR mutations from Asian patients (pts) with advanced lung adenocarcinoma (PIONEER). 2012, American Society of Clinical Oncology. [DOI:10.1200/jco.2012.30.15_suppl.1534]
23. Midha, A., S. Dearden, and R. McCormack, EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). American journal of cancer research, 2015. 5(9): p. 2892.
24. Soda, M., et al., Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 2007. 448(7153): p. 561-566. [DOI:10.1038/nature05945]
25. Johnson, B.E., et al., A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: The Lung Cancer Mutation Consortium (LCMC). 2013, American Society of Clinical Oncology. [DOI:10.1200/jco.2013.31.15_suppl.8019]
26. Kwak, E.L., et al., Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New England Journal of Medicine, 2010. 363(18): p. 1693-1703. [DOI:10.1056/NEJMoa1006448]
27. Desai, S., et al., A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives. Indian journal of cancer, 2013. 50(2): p. 80-86. [DOI:10.4103/0019-509X.117007]
28. Bergethon, K., et al., ROS1 rearrangements define a unique molecular class of lung cancers. Journal of clinical oncology, 2012. 30(8): p. 863-870. [DOI:10.1200/JCO.2011.35.6345]

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