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Oncol Lett. 2015 Oct;10(4):2176-2184. Epub 2015 Aug 12.

Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients.

Author information

1
GeneKor, Athens 15344, Greece.
2
Pulmonary Department, Oncology Unit, 'G. Papanikolaou' General Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
3
Oncology Unit, General Hospital of Kavala, Kavala 65500, Greece.
4
Department of Medical Oncology, University General Hospital of Alexandroupolis, Evros 68100, Greece.
5
Department of Thoracic Surgery, Athens Medical Center, Athens 30606, Greece.
6
University Clinic of Pulmonology, 'Sotiria' Chest Diseases Hospital, Athens 11527, Greece.
7
Department of Oncology, Evaggelismos Hospital, Athens 10676, Greece.
8
Second Pulmonary Clinic, 'Sotiria' Chest Diseases Hospital, Athens 11527, Greece.
9
Fifth Pulmonary Clinic, 'Sotiria' Chest Diseases Hospital, Athens 11527, Greece.
10
Department of Respiratory and Critical Care Medicine (KAA), 'Sotiria' Chest Diseases Hospital, Athens 11527, Greece.
11
Seventh Pulmonary Clinic, 'Sotiria' Chest Diseases Hospital, Athens 11527, Greece.
12
Second Department of Medical Oncology, 'Agii Anargiri' Cancer Hospital, Athens 11524, Greece.
13
Department of Medical Oncology, Medical School, Aristotle University, Papageorgiou Hospital, Thessaloniki 54124, Greece.
14
Second Department of Respiratory Medicine, Sismanoglio-A. Fleming General Hospital of Attiki, Athens 15126, Greece.

Abstract

It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18-21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of EGFR mutations. Furthermore, KRAS mutation analysis in patients with a known smoking history revealed no difference in mutation frequency according to smoking status; however, a different mutation spectrum was observed.

KEYWORDS:

Kirsten-rat sarcoma oncogene homolog; Sanger sequencing; epidermal growth factor receptor; high-resolution melting curve analysis; next generation sequencing; non-small-cell lung cancer

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