Mutational Damages in Malignant Lung Tumors

Abstract

Background: Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment. Methods: The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. Results:The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1-and Pst1-restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma. Conclusion: The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.

Targeted Inhibitors of EGFR: Structure, Biology, Biomarkers, and Clinical Applications

“…The two most common mutations of EGFR in NSCLC represent about 85–90% of all EGFR mutations [ 45 ]. The first one is a deletion of EGFR exon 19 ( del747–750 ), which eliminates the leucine-arginine-glutamate-alanine motif in the tyrosine kinase domain of EGFR ( LREA deletion ), and the second one ( L858R ) is a thymine-to-guanine transversion, which results in the replacement of leucine with arginine in exon 21 codon 858 [ 46 , 47 ]. The third most frequent type of EGFR mutations in NSCLC is exon 20 insertions (ex20ins), which constitute 9% [ 48 ]–12% [ 49 ] of all EGFR mutations.…”