Landscape of <i>KRAS</i>, <i>BRAF</i>,<i> PIK3CA</i> Genes Mutations and Clinical Features of EBV-Associated and MSI Gastric Cancer

Abstract

Personalization of gastric cancer treatment is an urgent problem due to clinical heterogeneity and aggressive course of the disease. In 2014, Cancer Genome Atlas researchers divided gastric cancers into four subtypes based on molecular characteristics: Epstein–Barr virus positive (EBV+), microsatellite instability (MSI), chromosomal instability, genomically stable. To date, there is no single method for detecting chromosomal instability and genomically stable subtypes, while MSI analysis and EBV assessment are used in routine practice and are of the greatest clinical importance. We analyzed 159 gastric cancer samples for the presence of MSI, EBV DNA, and somatic mutations in codons 12–13 (exon 2), 61 (exon 3), and 146 (exon 4) of the KRAS gene, codons 597–601 (exon 15) of the BRAF gene and codons 542–546 (exon 9), 1047–1049 (exon 20) of the PIK3CA gene. As a result, the EBV+ gastric cancer was detected in 8.2% of samples, MSI – in 13.2%. MSI and EBV+ were found to be mutually exclusive. The mean age of patients with EBV+ and MSI cancers was 54.8 and 62.1 years, respectively. In 92.3% of EBV+ cancer was detected in men, of which 76.2% were older than 50 years. diffuse and intestinal adenocarcinomas in EBV+ cancer accounted for 6 (46.2%) and 5 (38.5%) cases, respectively. MSI occurred in almost equal proportions in men and women (n = 10; 47.6%, n = 11; 52.4%), with a predominance of intestinal histological type (71.4%) and lesion of the lesser curvature (28.6%). One case of EBV+ cancer was diagnosed with the E545K variant in the PIK3CA gene. A combination of variants in the KRAS and PIK3CA genes was found in all MSI cases. The EBV+ subtype was associated with a better prognosis. Overall five-year survival rates for MSI and EBV+ cancers were 100.0 and 54.7%, respectively.