Extended?spectrum of KRAS and NRAS mutations in lung cancer tissue specimens obtained with bronchoscopy

ABSTRACT

Background: Mutations in the RAS genes, HRAS, KRAS, and NRAS, are the most common modifications in many types of human tumors and are found in approximately 30% of all human cancers. These mutations are usually found in codons 12, 13, or 61. Methods: The aim of this study is to evaluate mutations in codons 59, 117, and 146 of KRAS and NRAS genes in addition to codons 12,13, and 61 of KRAS gene in lung cancer tissue specimens obtained with bronchoscopy. KRAS and NRAS mutation analyses with pyrosequencing were performed on DNA isolated from formalin?fixed paraffin?embedded (FFPE) tissue samples of 64 patients histopathologically diagnosed as lung cancer after bronchoscopic biopsy. Results: In all, 20 patients (31.2%) had mutations in KRAS gene (8/27 squamous cell carcinoma, 8/11 adenocarcinoma, 3/16 small cell carcinoma, and 1/1 pleomorphic carcinoma). The most common mutation in codon 12 was in c.35G>T (G12V). When the mutation rate of adenocarcinoma (72.7%) and squamous cell carcinoma (22.9%) patients was compared with each other, a statistically significant difference was observed (P = 0.008). There were no mutations in codons 59, 117, or 146 of KRAS and NRAS genes in patients with lung cancer. Conclusion: In this study, we firstly examined mutations in codons 59, 117, and 146 of KRAS and NRAS genes in addition to codons 12, 13, and 61 of KRAS gene in Turkish lung cancer patients both in non?small cell lung cancer and small cell lung cancer. Although no mutation was detected in codons 59, 117, and 146 of KRAS and NRAS genes, the frequency of KRAS gene mutation was higher than the rate of mutation in both Asian and Western countries, and multicenter studies including more cases should be performed to further explore our results.