Spectra of germline and somatic mutations in diffuse and intestinal types of gastric cancer

Background. Gastric cancer (GC) is one of the most common oncological diseases, with the fifth place in the world in terms of morbidity and the third on mortality among all malignant neoplasms. Until recently, the classification of GC was based mainly on histological criteria. Objective. To characterize the spectra of gene mutations in various histological types of gastric tumors, and to search for novel mutations in the Russian patients. Material and methods. To analyze 52 GC samples and the samples of morphologically unaltered tissues from the same patients, we have used NGS with two panels, an Ion AmpliSeq Cancer Hotspot Panel v2, widely used for the analysis of «hot spots» in cancer related genes, and an in-house panel developed for sequencing the genes involved in gastric carcinogenesis. Results. In total, with two panels, we have identified 20 genetic variants with exceptionally low general population frequencies (no higher than 0.00004 according to the gnomAD database), and 19 genetic variants that have never been reported previously. We report a statistically significant enrichment of a cohort of intestinal tumors with somatic missense mutations in the TP53 gene compared to diffuse tumors. The germline status was determined for 4 novel genetic variants, in the RB1 , SMO and CDH1 genes.

рак желудка, мутации, секвенирование ДНК, NGS, Gastric cancer, mutations, DNA sequencing, NGS

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