DOI QR코드

DOI QR Code

Correlation between EGFR Gene Mutations and Lung Cancer: a Hospital-Based Study

  • Kavitha, Matam (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Iravathy, Goud (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Adi Maha, Lakshmi M (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Ravi, V (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Sridhar, K (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Vijayanand, Reddy P (Molecular Biology and Cytogenetics Department, Apollo Health city Building, Apollo Hospitals) ;
  • Chakravarthy, Srinivas (Department of Oncology, Apollo Hospitals) ;
  • Prasad, SVSS (Department of Oncology, Apollo Hospitals) ;
  • Tabassum, Shaik Nazia (Department of Pharmacy practice, Browns college of Pharmacy) ;
  • Shaik, Noor Ahmad (Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University) ;
  • Syed, Rabbani (Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University) ;
  • Alharbi, Khalid Khalaf (Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University) ;
  • Khan, Imran Ali (Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University)
  • Published : 2015.11.04

Abstract

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

Keywords

EFGR;NSCLC;TKI;DNA sequencing

References

  1. Cai G, Wong R, Chhieng D, et al (2013). Identification of EGFR mutation, KRAS mutation, and ALK gene rearrangement in cytological specimens of primary and metastatic lung adenocarcinoma. Cancer Cytopathol, 121, 500-7. https://doi.org/10.1002/cncy.21288
  2. Chang A, Parikh P, Thongprasert S, et al (2006). Gefitinib (IRESSA). in patients of Asian origin with refractory advanced non-small cell lung cancer: subset analysis from the ISEL study. J Thorac Oncol, 1, 847-55. https://doi.org/10.1016/S1556-0864(15)30415-9
  3. Cortes-Funes H, Gomez C, Rosell R, et al (2005). Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients. Ann Oncol, 16, 1081-6. https://doi.org/10.1093/annonc/mdi221
  4. David M Jackman, Beow Y Yeap, Lecia V Sequist Neal Lindeman, et al (2006). Exon 19 deletion mutations of epidermal growth factor receptor are associated with prolonged survival in non-small cell lung cancer patients treated with gefitinib or erlotinib. Clin Cancer Res, 12, 3908. https://doi.org/10.1158/1078-0432.CCR-06-0462
  5. Dong J, Hu Z, Wu C, et al (2012). Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population. Nat Genet, 44, 895-9. https://doi.org/10.1038/ng.2351
  6. Ettinger DS, Akerley W, Bepler G, et al (2010). Non-small cell lung cancer. J Natl Compr Canc Netw, 8, 740-801.
  7. He J, Deng L, Na F, et al (2014). The association between TGF-${\beta}$1 polymorphisms and radiation pneumonia in lung cancer patients treated with definitive radiotherapy: a metaanalysis. PLoS One, 9, 91100. https://doi.org/10.1371/journal.pone.0091100
  8. He P, Yang XX, He XQ, et al (2014). CHRNA3 polymorphism modifies lung adenocarcinoma risk in the Chinese han population. Int J Mol Sci, 15, 5446-57. https://doi.org/10.3390/ijms15045446
  9. Izar B, Sequist L, Lee M, et al (2013). The impact of EGFR mutation status on outcomes in patients with resected stage I non-small cell lung cancers. Ann Thorac Surg, 96, 962-8. https://doi.org/10.1016/j.athoracsur.2013.05.091
  10. Jin F, Qian C, Qing Y, et al (2014). Genetic polymorphism of APE1 rs1130409 can contribute to the risk of lung cancer. Tumour Biol, 35, 6665-71. https://doi.org/10.1007/s13277-014-1829-9
  11. Jou YS, Lo YL, Hsiao CF, et al (2009). Association of an EGFR intron 1 SNP with never smoking female lung adenocarcinoma patients. Lung Cancer, 64, 251-6. https://doi.org/10.1016/j.lungcan.2008.09.014
  12. Kosaka T, Yatabe Y, Endoh H, et al (2004). Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res, 64, 8919-8923. https://doi.org/10.1158/0008-5472.CAN-04-2818
  13. Liu W, He L, Ramirez J, et al (2011). Functional EGFR germ line polymorphisms may confer risk for EGFR somatic mutations in non-small cell lung cancer, with a predominant effect on exon 19 microdeletions. Cancer Res, 71, 2423-7. https://doi.org/10.1158/0008-5472.CAN-10-2689
  14. Fukuoka M, Yano S, Giaccone G, et al (2003). Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (the IDEAL trial). J Clin Oncol, 21, 2237-46. https://doi.org/10.1200/JCO.2003.10.038
  15. Khan IA, Shaik NA, Kamineni V, et al (2015). Evaluation of gestational diabetes mellitus risk in south indian women based on MTHFR (C677T) and FVL (G1691A) mutations. Front Pediatr, 34, 1-5.
  16. Khan IA, Shaik NA, Pasupuleti N, et al (2015a). Screening of mitochondrial mutations and insertion-deletion polymorphism in gestational diabetes mellitus in the Asian Indian population. Saudi J Bio Sci, 22, 243-8. https://doi.org/10.1016/j.sjbs.2014.11.001
  17. Kris MG, Natale RB, Herbst RS, et al (2003). Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. J Am Med Assoc, 290, 2149-58. https://doi.org/10.1001/jama.290.16.2149
  18. Marchetti A, Martella C, Felicioni L, et al (2005). EGFR mutations in non- small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment. J Clin Oncol, 23, 857-65. https://doi.org/10.1200/JCO.2005.08.043
  19. Noronha V, Prabhash K, Thavamani A, et al (2013). EGFR mutations in Indian lung cancer patients: clinical correlation and outcome to EGFR targeted therapy. PLoS ONE, 8, 61561. https://doi.org/10.1371/journal.pone.0061561
  20. Paez JG, Janne PA, Lee JC, et al (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304, 1497-500. https://doi.org/10.1126/science.1099314
  21. Pao W, Miller V, Zakowski M, et al (2004). EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA, 101, 13306-11. https://doi.org/10.1073/pnas.0405220101
  22. Powrozek T, Krawczyk P, Ramlau R, et al (2014). EGFR gene mutations in patients with adenosquamous lung carcinoma. Asia Pac J Clin Oncol, 10, 340-5. https://doi.org/10.1111/ajco.12177
  23. Reinersman JM, Johnson ML, Riely GJ, et al (2010). Frequency of EGFR and KRAS mutations in lung adenocarcinomas in African Americans. J Thorac Oncol, 6, 28-31.
  24. Rosell R, Moran T, Queralt C, et al (2009). Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med, 361, 958-67. https://doi.org/10.1056/NEJMoa0904554
  25. Sahoo R, Harini VV, Babu VC, et al (2011). Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer, 73, 316-9. https://doi.org/10.1016/j.lungcan.2011.01.004
  26. Shigematsu H, Lin L, Takahashi T, et al (2005). Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst, 97, 339-46. https://doi.org/10.1093/jnci/dji055
  27. Shitara M, Sasaki H, Yokota K, et al (2012). Polymorphisms in intron 1 of the EGFR gene in non-small cell lung cancer patients. Exp Ther Med, 4, 785-9.
  28. Sun PL, Seol H, Lee HJ, et al (2012). High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol, 7, 323-30. https://doi.org/10.1097/JTO.0b013e3182381515
  29. Suzuki M, Kageyama S, Shinmura K, et al (2008). Inverse relationship between the length of the EGFR CA repeat polymorphism in lung carcinoma and protein expression of EGFR in the carcinoma. J Surg Oncol, 98, 457-461. https://doi.org/10.1002/jso.21130
  30. Thunnissen E, van der Oord K, den Bakker M (2014). Prognostic and predictive biomarkers in lung cancer. A review. Virchows Arch, 464, 347-58. https://doi.org/10.1007/s00428-014-1535-4
  31. Tokumo M, Toyooka S, Kiura K, et al (2005). The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res, 11, 1167-73.
  32. Ueno T, Toyooka S, Suda K, Soh J, Yatabe Y, Miyoshi S, Matsuo K, Mitsudomi T. et al (2012). Impact of age on epidermal growth factor receptor mutation in lung cancer. Lung Cancer, 78, 207-11. https://doi.org/10.1016/j.lungcan.2012.09.006
  33. Varalakshmi K (2013). Classification of lung cancer nodules using a hybrid approach. J Emerg Trends Comput Informat Sci, 4, 63-68.
  34. Wang B, Zhang L, Qiu F, et al (2014). A newfound association between mdc1 functional polymorphism and lung cancer risk in Chinese. PLoS One, 9, 106794. https://doi.org/10.1371/journal.pone.0106794
  35. Wang Y, Wenlong B, Hua S, et al (2013). Epidermal growth factor receptor exon 20 mutation increased in post-chemotherapy patients with non-small cell lung cancer detected with patients’ blood samples. Transl Oncol, 4, 504-10.
  36. Zhao Y, Wei Q, Hu L, et al (2014). Polymorphisms in microRNAs are associated with survival in non-small cell lung cancer. Cancer Epidemiol Biomarkers Prev, 23, 2503-11. https://doi.org/10.1158/1055-9965.EPI-14-0389

Cited by

  1. Prevalence and Clinical Profile of EGFR Mutation In Non-Small-Cell Lung Carcinoma Patients in Southwest China vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.965