[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.7314/APJCP.2015.16.16.7071

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)

Publication Information

Asian Pacific Journal of Cancer Prevention / v.16, no.16, 2015 , pp. 7071-7076 More about this Journal

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;

Citations & Related Records

Reference

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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
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	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. DOI
17	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. DOI
18	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. DOI
19	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. DOI
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. DOI
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. DOI
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. DOI
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	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.
25	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. DOI
26	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. DOI
27	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. DOI
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. DOI
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. DOI
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. DOI
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. DOI
33	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. DOI
34	Varalakshmi K (2013). Classification of lung cancer nodules using a hybrid approach. J Emerg Trends Comput Informat Sci, 4, 63-68.
35	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. DOI
36	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.