P53 and EGFR gene mutations
 in malignant tumors of the lung

Abstract

Relevance: Increased incidence of lung cancer globally
 and in Kazakhstan, lack of screening in hereditary cases, high
 mortality, and low survival of patients necessitate the study of
 the molecular genetic causes of the disease. At present, gene
 mutation studies for lung cancer diagnostics are expanding.
 However, many gene mutations revealed remain undercovered
 in the scientific literature, and there is not enough data on their
 prognostic and diagnostic value.
 The purpose of the study was to discover the specifics of
 the р53 gene mutations and reveal the EGFR exon 19 deletions
 and exon 21 L858R mutations in malignant tumors of the lung
 of various histogenesis.
 Methods: The mutations were studied in tumors (200 samples) and adjacent tissue (200 samples) of patients with lung
 cancer (squamous cell carcinoma (SCC) and adenocarcinoma
 (ADC) of the lung) by polymerase chain reaction (PCR), electrophoresis, and EcoR1- and Pst1-restriction of samples after p53
 gene fragments and cDNA amplification and mRNA revertase
 treatment. Another 263 lung cancer samples were evaluated
 by real-time PCR for EGFR exon 19 deletions and EGFR exon 21
 L858R mutations.
 Results: The p53 gene was not expressed in 50% of SCC and
 adenocarcinoma of the lung samples. Restriction revealed p53
 mRNA mutations in 100% of SCC and 75% of ADC samples. p53
 exon-intron 5-6 was mutated in 50% of ADC and 70% of SCC
 samples, exon-intron 7-9 – in 60% of SCC cases. EGFR exons 19
 and 21 mutations found in 65 of 263 lung tumor samples were
 associated with increased sensitivity to EGFR tyrosine kinase
 inhibitors.
 Conclusion: The p53 gene mutations revealed in most
 samples of SCC and ADC of the lung could be used to diagnose
 lung cancer and predict its severity. The identified EGFR mutations allow predicting the effectiveness of targeted therapy