Analysis of the relationship of somatic mutations with the development of leukoplakia and squamous cell carcinoma of the oral mucosa

The molecular genetic basis for pathogenesis of leukoplakia and squamous cell carcinoma of the oral mucosa (OM) is not well understood. Few studies are devoted to this problem and their results are incomplete and contradictory. At the same time, the early diagnosis of OM cancer and the prediction of its development are important public health problems.The aim of the study was to analyze the relationship of somatic mutations with the formation of leukoplakia and squamous cell carcinoma of the oral mucosa.48 altered OM epithelium samples of patients with OM leukoplakia (OML) (24 samples) and OM squamous cell carcinoma (OMSCC) (24 samples) were taken as material for research.The pathogenic and probably pathogenic variants of the TP53, NRAS, and BRAF genes identified in this study, both  as one by one and in combination, are associated with high probability (RR 3000‒11 000) with OML with grade 1 epithelial squamous intraepithelial neoplasia. Identified pathogenic and probably pathogenic variants of the ERCC3, HOXB13, KRAS, MSH3, MSH6, PIK3CA, and TP53 genes are associated with a high probability (RR 90‒22 000) with the OMSCC development. The observed pathogenic variants of the KRAS and TP53 genes are highly likely to lead to the formation of OML with grade 1 squamous intraepithelial neoplasia of the epithelium; a subsequent formation of pathogenic variants of the PIC3CA and/or HOXB13 and MSH3 genes leads to malignant transformation of altered OM epithelial cells ( p = 0.0000048). This information allows designing PCR-and NGS-test systems for predicting the development and early diagnosis of OMSCC.