Potential Effects of EGFR Exon 21 L858R Mutations in Lung Cancer
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Published:
Feb 28, 2019
Keywords:
exon 21 EGFR gene Lung cancer
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Abstract
Objective: The mainly significant reason in the etiology of lung cancer is smoking, which is important in other environmental pollutants and genetic susceptibility. Lung cancer is separated two major groups as mainly non-small cell and small cell according to the growth rate, spread, timing of metastasis, response to chemotherapy and radiotherapy. Epidermal growth factor receptor (EGFR) constitutes the highest rate with 50-80% in gene mutations which are prognostic value in lung cancer. Many studies have shown that EGFR is overexpressed in lung cancer. In our study, we aimed to investigate the relationship between EGFR gene exon 21 L858R mutations in lung cancer.
Material and Methods: Our sample consisted of a healthy group of 190 healthy volunteers with the same age and gender characteristics as the patient group of 178 patients who were diagnosed as lung cancer in the Mersin University Medical Faculty Oncology clinic. The DNAs were obtained according to the standard salt precipitation method. Mutation detection and genotyping analyzes were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyzes.
Results: Smoking was one of the other risk factors for lung cancer, 130 (68.33%) in the control group and 156 (87.5%) in the lung cancer group. 27 person of the lung cancer (15%) were female and 151 (85%) were male. In the control group, 92 people (48.33%) were in the wild genotype and 98 persons were in the mutant genotype (51.66%). In the lung cancer group 80 (45%) were wild-type and 98 (55%) were mutant genotypes. According to the histopathological types of lung cancer, EGFR-21 mutation heterozygous or homozygous carriers are proportionally compatible (p = 0.90).
Conclusion: According to our findings, the EGFR-21 mutation is not associated with histopathological types of lung cancer.
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Eker, E. D., Arıcan, A., Arpacı, R. B. ., Nayır, E., Ata, A. ., Eras, N. ., Yıldırım, D. D., & Akbaş, E. . (2019). Potential Effects of EGFR Exon 21 L858R Mutations in Lung Cancer. Medical Science and Discovery, 6(2), 12–17. Retrieved from https://medscidiscovery.com/index.php/msd/article/view/198
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Research Article
References
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35. Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J Clin Oncol 2016; 34:721-730
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37. Lee JS, Kim HR, Lee CY, Shin M, Shim HS. EGFR and TTF-1 gene amplification in surgically resected lung adenocarcinomas: clinicopathologic significance and effect on response to EGFR-tyrosine kinase inhibitors in recurred cases. Ann Surg Oncol. 2013; 20(9):3015-22.
38. Kawada I, Soejima K, Watanabe H, Nakachi I, Yasuda H, Naoki K, et al. An Alternative Method for Screening EGFR Mutation Using RFLP in Non-small Cell Lung Cancer Patients. J Thorac Oncol. 2008; 3:1096–1103.
39. Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P. Risk factors for lung cancer worldwide. Eur Respir J. 2016; 48(3):889-902
40. de Groot P, Munden RF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am. 2012; 50(5):863-76.
41. Akhtar N, Bansal JG. Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer. 2017; 41(5):328-339.
42. Lin H, Huang YS, Yan HH, Yang XN, Zhong WZ, et al. A family history of cancer and lung cancer risk in never-smokers: A clinic-based case-control study. Lung Cancer. 2015; 89(2):94-8.
43. Bethune G,Bethune D, Ridgway N,Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010; 2(1):48–51.
44. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3:215-224.
45. Bartholomew C, Eastlake L, Dunn P, Yiannakis D. EGFR targeted therapy in lung cancer; an evolving story. Respir Med Case Rep. 2017; 20:137-140.
46. Rudin CM, Avila-Tang E, Harris CC, Herman CG, Hirsch FR, Pao W, et al. Lung Cancer in Never Smokers: Molecular Profiles And Therapeutic Implications. Clin Cancer Res. 2009; 15(18):5646–5661.
47. Tseng CG, Chiang CJ, Tseng JS, Yang TY, Hsu KH, Chen KC et al. EGFR mutation, smoking, and gender in advanced lung adenocarcinoma. Oncotarget. 2017; 8(58):98384–98393.
48. https://www.iaslc.org/articles/high-frequency-egfr-mutations-found-asian-population Accessed 21.11.2018
2. Sasaki K, Kawauchi S. Molecular cytogenetic analysis of solid tumors. J Orthop Sci 2003; 8:457-9.
3. http://www.who.int/cancer/en/ Accessed 21.11.2018
4. www.cancerquest.org Accessed 21.11.2018
5. Jemal A, Tiwari RC, Murray T et al. Cancer statistics, 2004. CA Cancer J Clin 2004; 54:8-29.
6. Akciğer ve Plevra Maligniteleri Çalışma Grubu. Akciğer kanseri tanı ve tedavi rehberi. Toraks Dergisi 2006; 7:1-37.
7. Alberg AJ, Ford JG, Samet JM. Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132:29-55.
8. Grenle RT, Murray T, Bolden, S, Wingo PA. Cancer statistics 2000. CA, Cancer J Clin 2000; 50:7-33.
9. Kumar V, Cotran RS, Robbins SL. Temel Patoloji, 2000. 6. baskı, NobelTıp Kitabevi, İstanbul.
10. www.patoloji.gen.tr Accessed 21.11.2018
11. Cooper WA, Lam DC, O'Toole SA, Minna JD. Molecular biology of lung cancer. J Thorac Dis. 2013; 5:479-90.
12. Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS Journal 2010; 277(2): 301-308.
13. Siegelin MD, Borczuk AC. Epidermal growth factor receptor mutations in lung adenocarcinoma. Laboratory Investigation. 2014; 94:129–137.
14. Bozetti C, Tiseo M, Lagrasta C, Nizzolli R, Guazzi A, et al. Comparison between epidermal growth factor receptor gene expression in primary non small cell lung cancer and in fine-needle aspirate from distant metastatic sites. J Thorac Oncol. 2008; 3(1):18-22.
15. Takano T, Ohe Y, Sakamoto H et al. Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. J Clin Oncol 2005; 23:6829-37.
16. Hung WY, Chang JH, Cheng Y, Chen CK, Chen JQ, Hua KT, Cheng CW, Hsiao M, Chung CL, Lee WJ, Chien MH. Leukocyte Cell-Derived Chemotaxin 2 Retards Non-Small Cell Lung Cancer Progression Through Antagonizing MET and EGFR Activities. Cell Physiol Biochem. 2018; 51(1):337-355.
17. Agustoni F, Suda K, Yu H, Ren S, Rivard CJ, Ellison K, Caldwell C Jr, Rozeboom L, Brovsky K, Hirsch FR. EGFR-directed monoclonal antibodies in combination with chemotherapy for treatment of non-small-cell lung cancer: an updated review of clinical trials and new perspectives in biomarkers analysis. Cancer Treat Rev. 2018; 4(72):15-27.
18. Han SW, Kim TY, Hwang PG et al. Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol 2005; 23:2493-501.
19. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 2007; 25:587-95.
20. Liu C, Xu X, Zhou Y. Association between EGFR polymorphisms and the risk of lung cancer. Int J Clin Exp Pathol. 2015; 8(11):15245-9.
21. Han F, He J, Li F, Yang J, Wei J, Cho WC, Liu X. Emerging Roles of MicroRNAs in EGFR-Targeted Therapies for Lung Cancer. Biomed Res Int. 2015; 672759-69.
22. Baldacci S, Kherrouche Z, Cockenpot V, Stoven L, Copin MC, Werkmeister E, Marchand N, Kyheng M, Tulasne D, Cortot AB. MET amplification increases the metastatic spread of EGFR-mutated NSCLC. Lung Cancer. 2018; 125:57-67.
23. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells Nucleic Acids Res 1988; 16:1215.
24. Bircan S, Baloglu H, Kucukodaci Z, et al. EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. MedOncol. 2014; 31:87.
25. Li M, Zhang Q, Liu L, et al. The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China. Neoplasma. 2011; 58:74-81.
26. Quan X, Gao H, Wang Z, et al. Epidermal Growth Factor Receptor Somatic Mutation Analysis in 354 Chinese Patients with Non Small Cell Lung Cancer. Oncology Letters. 2018; 15:2131-2138.
27. Su J, Zhong W, Zhang X, et al. Molecular characteristics and clinical outcomes of EGFR exon 19 in del subtypes to EGFR TKIs in NSCLC patients. Oncotarget. 2017; 8:111246-111257.
28. Yener NA, Apa DD. Akciğer kanserinde morfolojik tanı ve sınıflama. Trd Sem 2014; 2:281-289.
29. Meyerson M, Carbone D. Genomic and proteomic profiling of lung cancers: lung cancer classification in the age of targeted therapy. J Clin Oncol. 2005; 23(14):3219-26.
30. Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: Biology and treatment options. Biochim Biophys Acta. 2015; 1856(2):189-210.
31. Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J. Clin. Oncol 2013; 31(8):992-1001.
32. Shtivelman E, Hensing T, Simon GR, Dennis PA, Otterson GA, Bueno R, Salgia R. Molecular pathways and therapeutic targets in lung cancer. Oncotarget 2014; 5(6):1392-1433.
33. Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res. 2016; 5(3):288-300.
34. Baek JH, Sun JM, Min YJ, et al. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated nonsmall cell lung cancer except both exon 19 deletion and exon 21 L858R: A retrospective analysis in Korea. Lung Cancer. 2015; 87:148-154.
35. Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. J Clin Oncol 2016; 34:721-730
36. Sandra P, D'Angelo M, Pietanza C, et al. Incidence of EGFR Exon 19 Deletions and L858R in Tumor Specimens From Men and Cigarette Smokers With Lung Adenocarcinomas. J ClinOncol 2011; 10:2066-2070.
37. Lee JS, Kim HR, Lee CY, Shin M, Shim HS. EGFR and TTF-1 gene amplification in surgically resected lung adenocarcinomas: clinicopathologic significance and effect on response to EGFR-tyrosine kinase inhibitors in recurred cases. Ann Surg Oncol. 2013; 20(9):3015-22.
38. Kawada I, Soejima K, Watanabe H, Nakachi I, Yasuda H, Naoki K, et al. An Alternative Method for Screening EGFR Mutation Using RFLP in Non-small Cell Lung Cancer Patients. J Thorac Oncol. 2008; 3:1096–1103.
39. Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P. Risk factors for lung cancer worldwide. Eur Respir J. 2016; 48(3):889-902
40. de Groot P, Munden RF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am. 2012; 50(5):863-76.
41. Akhtar N, Bansal JG. Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer. 2017; 41(5):328-339.
42. Lin H, Huang YS, Yan HH, Yang XN, Zhong WZ, et al. A family history of cancer and lung cancer risk in never-smokers: A clinic-based case-control study. Lung Cancer. 2015; 89(2):94-8.
43. Bethune G,Bethune D, Ridgway N,Xu Z. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010; 2(1):48–51.
44. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential role of cetuximab. Biologics. 2009; 3:215-224.
45. Bartholomew C, Eastlake L, Dunn P, Yiannakis D. EGFR targeted therapy in lung cancer; an evolving story. Respir Med Case Rep. 2017; 20:137-140.
46. Rudin CM, Avila-Tang E, Harris CC, Herman CG, Hirsch FR, Pao W, et al. Lung Cancer in Never Smokers: Molecular Profiles And Therapeutic Implications. Clin Cancer Res. 2009; 15(18):5646–5661.
47. Tseng CG, Chiang CJ, Tseng JS, Yang TY, Hsu KH, Chen KC et al. EGFR mutation, smoking, and gender in advanced lung adenocarcinoma. Oncotarget. 2017; 8(58):98384–98393.
48. https://www.iaslc.org/articles/high-frequency-egfr-mutations-found-asian-population Accessed 21.11.2018