https://doi.org/10.4081/monaldi.2024.3202
Common epidermal growth factor receptor mutations in north Indian patients with non-small cell lung carcinoma: evidence from real-time polymerase chain reaction
Submitted: September 12, 2024
Accepted: September 13, 2024
Published: October 25, 2024
Accepted: September 13, 2024
Abstract Views: 705
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Lung carcinoma was the ace cause of cancer deaths globally in 2022, with non-small cell lung carcinoma (NSCLC) accounting for 81% of the burden. Due to promising tyrosine kinase inhibitor (TKI) trials, NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations are of interest. Our aim was to determine EGFR mutation prevalence in north India and its histologic and demographic correlations. We investigated the frequency of EGFR mutations in 40 patients with histologically confirmed NSCLC using real-time polymerase chain reaction. A 15% mutation frequency was observed in the study sample, involving 32 males and 8 females with a median age of 59 years. Squamous cell carcinoma (SCC) patients had only EXON20 (T790M, exon20 insertion) mutations, while adenocarcinoma patients had mutations in both EXON20 (T790M) and 21 (L858R) with mutation frequencies of 22% and 10%, respectively. 28% of the SCC patients were non-smokers, and 60% of these non-smokers had an EGFR mutation. South Indian and Asian studies have identified EXON19 (19-Del) and EXON21 (L858R) mutations as “common mutations” that account for nearly 80-90% of all mutations and respond well to TKIs. Interestingly, “common mutations” were found seldom in our study population, while the uncommon variants constitute 83% of all mutations, which we assume is due to diverse Indian genetics and ethnicity and co-existing signature mutations that involve the tyrosine kinase domain of EXON20. We suggest future genome-wide association studies to identify plausible genetic polymorphisms responsible for interethnic differences in EGFR mutation, which will contribute to better treatment and prevention of NSCLCs.
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024;74:229-63.
DOI: https://doi.org/10.3322/caac.21834
Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin 2022;72:7-33.
DOI: https://doi.org/10.3322/caac.21708
Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380-8.
DOI: https://doi.org/10.1056/NEJMoa0909530
Xu J, Yang H, Jin B, et al. EGFR tyrosine kinase inhibitors versus chemotherapy as first-line therapy for non-small cell lung cancer patients with the L858R point mutation. Sci Rep 2016;6:36371.
DOI: https://doi.org/10.1038/srep36371
Noronha V, Prabhash K, Thavamani A, et al. EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.
DOI: https://doi.org/10.1371/journal.pone.0061561
Bhatt AD, Pai R, Rebekah G, et al. Clinicopathologic features of non-small cell lung cancer in India and correlation with epidermal growth factor receptor mutational status. Indian J Cancer 2013;50:94-101.
DOI: https://doi.org/10.4103/0019-509X.117016
Tarigopula A, Ramasubban G, Chandrashekar V, et al. EGFR mutations and ROS1 and ALK rearrangements in a large series of non-small cell lung cancer in South India. Cancer Rep 2020;3:e1288.
DOI: https://doi.org/10.1002/cnr2.1288
Kasana BA, Dar WR, Aziz SA, et al. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: prevalence and relation with different clinical variables. Indian J Med Paediatr Oncol 2016;37:189-95.
DOI: https://doi.org/10.4103/0971-5851.190356
Bal A, Singh N, Agarwal P, et al. ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India. APMIS 2016;124:832-8.
DOI: https://doi.org/10.1111/apm.12581
Shigematsu H, Minna JD, Gazdar AF. Response Re: Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2006;98:363-4.
DOI: https://doi.org/10.1093/jnci/djj075
Voldborg BR, Damstrup L, Spang-Thomsen M, et al. Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 1997;8:1197-206.
DOI: https://doi.org/10.1023/A:1008209720526
O’Leary C, Gasper H, Sahin KB, et al. Epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Pharmaceuticals 2020;13:273.
DOI: https://doi.org/10.3390/ph13100273
Bethune G, Bethune D, Ridgway N, et al. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis 2010;2:48-51.
Sholl LM, Yeap BY, Iafrate AJ, et al. Lung adenocarcinoma with EGFR amplification has distinct clinicopathologic and molecular features in never-smokers. Cancer Res 2009;69:8341-8.
DOI: https://doi.org/10.1158/0008-5472.CAN-09-2477
Gupta R, Dastane AM, McKenna R Jr, et al. The predictive value of epidermal growth factor receptor tests in patients with pulmonary adenocarcinoma: review of current “best evidence” with meta-analysis. Hum Pathol 2009;40:356-65.
DOI: https://doi.org/10.1016/j.humpath.2008.08.008
He C, Wei C, Wen J, et al. Comprehensive analysis of NGS and ARMS-PCR for detecting EGFR mutations based on 4467 cases of NSCLC patients. J Cancer Res Clin Oncol 2022;148:321-30.
DOI: https://doi.org/10.1007/s00432-021-03818-w
Li AR, Chitale D, Riely GJ, et al. EGFR Mutations in Lung Adenocarcinomas. J Mol Diagn 2008;10:242-8.
DOI: https://doi.org/10.2353/jmoldx.2008.070178
Yoon H-Y, Ryu J-S, Sim YS, et al. Clinical significance of EGFR mutation types in lung adenocarcinoma: a multi-centre Korean study. PLoS One 2020;15:e0228925.
DOI: https://doi.org/10.1371/journal.pone.0228925
Chiu CH, Yang CT, Shih JY, et al. Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced lung adenocarcinomas with G719X/L861Q/S768I mutations. J Thorac Oncol 2015;10:793-9.
DOI: https://doi.org/10.1097/JTO.0000000000000504
Metro G, Crinò L. Advances on EGFR mutation for lung cancer. Transl Lung Cancer Res 2012;1:5-13.
Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget 2016;7:78985-93.
DOI: https://doi.org/10.18632/oncotarget.12587
Graham RP, Treece AL, Lindeman NI, et al. Worldwide frequency of commonly detected EGFR mutations. Arch Pathol Lab Med 2018;142:163-7.
DOI: https://doi.org/10.5858/arpa.2016-0579-CP
Tanaka T, Matsuoka M, Sutani A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 2010;126:651-5.
DOI: https://doi.org/10.1002/ijc.24746
Singh N, Agrawal S, Jiwnani S, et al. Lung cancer in India. J Thorac Oncol 2021;16:1250-66.
DOI: https://doi.org/10.1016/j.jtho.2021.02.004
Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med 2008;359:1367-80.
DOI: https://doi.org/10.1056/NEJMra0802714
Joshi A, Zanwar S, Noronha V, et al. EGFR mutation in squamous cell carcinoma of the lung: does it carry the same connotation as in adenocarcinomas? Onco Targets Ther 2017;10:1859-63.
DOI: https://doi.org/10.2147/OTT.S125397
Ho HL, Kao HL, Yeh YC, et al. The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies. Diagn Pathol 2019;14:59.
DOI: https://doi.org/10.1186/s13000-019-0840-2
Zhang Q, Zhu L, Zhang J. Epidermal growth factor receptor gene mutation status in pure squamous-cell lung cancer in Chinese patients. BMC Cancer 2015;15:88.
DOI: https://doi.org/10.1186/s12885-015-1056-9
Anusewicz D, Orzechowska M, Bednarek AK. Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling. Sci Rep 2020;10:21128.
DOI: https://doi.org/10.1038/s41598-020-77284-8
Arrieta O, Cardona AF, Martín C, et al. Updated frequency of EGFR and KRAS mutations in nonsmall-cell lung cancer in Latin America: the Latin-American consortium for the investigation of lung cancer (CLICaP). J Thorac Oncol 2015;10:838-43.
DOI: https://doi.org/10.1097/JTO.0000000000000481
Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359:366-77.
DOI: https://doi.org/10.1056/NEJMoa0800668
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57.
DOI: https://doi.org/10.1056/NEJMoa0810699
Ye L, Mesbah Ardakani N, Thomas C, et al. Detection of low-level EGFR c.2369 C > T (p.Thr790Met) resistance mutation in pre-treatment non-small cell lung carcinomas harboring activating EGFR mutations and correlation with clinical outcomes. Pathol Oncol Res 2020;26:2371-9.
DOI: https://doi.org/10.1007/s12253-020-00833-z
Inukai M, Toyooka S, Ito S, et al. Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 2006;66:7854-8.
DOI: https://doi.org/10.1158/0008-5472.CAN-06-1951
Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol 2012;30:433-40.
DOI: https://doi.org/10.1200/JCO.2011.38.3224
Ethics Approval
Ethical clearance obtained from the Institutional Ethics Committee, VMMC, and Safdarjung Hospital, New Delhi with serial no IEC/VMMC/SJH/Thesis/06/2022/CC-233 dated 11th July 2022.How to Cite
Behera, Rakesh, Sheetal Arora, Pranav Ish, and Geetika Khanna. 2024. “Common Epidermal Growth Factor Receptor Mutations in North Indian Patients With Non-Small Cell Lung Carcinoma: Evidence from Real-Time Polymerase Chain Reaction”. Monaldi Archives for Chest Disease, October. https://doi.org/10.4081/monaldi.2024.3202.
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