СОМАТИЧЕСКИЕ МУТАЦИИ ПРИ ЛЕЙКОПЛАКИИ СЛИЗИСТОЙ ОБОЛОЧКИ РОТОВОЙ ПОЛОСТИ

Abstract

Introduction. Genetic basis for the development of leukoplakia of the oral mucosa is not well understood. Early prediction of oral mucosa cancer development is an important public health problem, which results in the importance of studying the pathogenesis of precancerous diseases. Malignant neoplasms of oral mucosa are mainly the cases of squamous cell carcinoma which commonly develops as the outcome of previous potentially malignant diseases, the leading of which is oral mucosa leukoplakia. Aim. The goal of study is to determine pathogenic somatic mutations in patients with oral mucosa leukoplakia and grade 1 epithelial dysplasia. Material and methods. We have studied 24 samples of altered epithelium of patients with oral mucosa leukoplakia. The QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used to isolate deoxyribonucleic acid from the samples. Sequencing was performed with Illumina NextSeq 550 sequencer and TruSight™ Oncology 500 DNA Kit (Illumina, USA). All operations for deoxyribonucleic acid extraction, sampling and sequencing were performed step by step in strict accordance with the instructions supplied with the reagent kits. Bioinformatic analysis was performed using Illumina BaseSpace and Galaxy Project software in accordance with current guidelines. Results and discussion. Pathogenic and probably pathogenic somatic mutations identified during this study in TP53, KRAS, APC, NRAS and BRAF genes, both singly and in combination, are reliably (risk ratios 3000-11000) associated with the development of leukoplakia of the oral mucosa with epithelial dysplasia of 1st degree. The multiplicity of genetic variants associated with epithelial dysplasia, as well as the fact that a number of variants do not occur in all patients simultaneously, suggests that the same histotype of oral mucosa dysplasia may develop under the influence of various mutations. Conclusion. Pathogenic and probably pathogenic variants of TP53, KRAS, APC, NRAS and BRAF genes, both singly and in combinations, are reliably associated with the development of leukoplakia of the oral mucosa with epithelial dysplasia of 1st degree (risk ratios 3000-11000).