Molecular genetic characteristics of non-small cell lung cancer using multi-target single-base elongation and fragment analysis


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Background. Lung cancer is the most frequent cause of cancer mortality. The prevailing type is non-small cell lung cancer (NSCLC), in the treatment of which EGFR tyrosine kinase inhibitors are actively used, as well as a combination of BRAF and MEK inhibitors. The indication for the targeted therapy is the genotyping of tumor samples for the detection of predictive markers, such as mutations in the EGFR, KRAS, BRAF and HER2 genes. One approach to the rapid and complex identification of aberrations in the genes of interest is the use of methods with high sensitivity: multi-target single-base elongation (MSE) and fragment analysis (FA). Objective. Determination of clinicopathological characteristics of patients with NSCLC with the presence of driver mutations in the EGFR, KRAS, BRAF and HER2 genes. Materials and methods. A cryobank of biological specimens taken from patients with NSCLC was organized at Pavlov First Saint Petersburg State Medical University. For genotyping of the central sites of tumor samples from 60 patients with NSCLC were used multi-target single-base elongation and fragment analysis. Results. EGFR mutations were found exclusively in patients with lung adenocarcinoma (p=0,0008) with a frequency of 31%. These aberrations are significantly associated with female gender (p=0,0002) and the absence of smoking status (p=0,0007). The ratio of exon 19 deletion to L858R was 2,5:1. The prevalence of minor mutations in EGFR-positive patients was 22,2%. Thus, the coexistence of minor mutations G719S and S768I was revealed in one tumor sample. The cause of acquired resistance to the first-generation EGFR TKI in a patient with exon 19 deletion was determined - T790M in the EGFR gene. KRAS mutations were found in 10% of male patients with NSCLC who was a current or former smoker. V600E in the BRAF gene and insertions in the HER2 gene were not detected. Conclusion. An integrated methodological approach allows to accurately determine clinically significant aberrations in the EGFR, KRAS, BRAF and HER2 genes in NSCLC patients according to the recommendations.

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作者简介

A. Musaelyan

Pavlov First Saint-Petersburg State Medical University

Email: a.musaelyan8@gmail.com

V. Nazarov

Pavlov First Saint-Petersburg State Medical University

S. Lapin

Pavlov First Saint-Petersburg State Medical University

I. Chistyakov

Pavlov First Saint-Petersburg State Medical University

I. Komarov

Pavlov First Saint-Petersburg State Medical University

O. Tkachenko

Pavlov First Saint-Petersburg State Medical University

M. Sogoyan

Pavlov First Saint-Petersburg State Medical University

E. Berdnik

Pavlov First Saint-Petersburg State Medical University

A. Mazing

Pavlov First Saint-Petersburg State Medical University

W. Emanuel

Pavlov First Saint-Petersburg State Medical University

A. Akopov

Pavlov First Saint-Petersburg State Medical University

S. Orlov

Pavlov First Saint-Petersburg State Medical University

S. Bagnenko

Pavlov First Saint-Petersburg State Medical University

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