Genetic analysis of fundic gland‑type gastric adenocarcinoma

This study aimed to analyze the molecular characteristics of gastric adenocarcinoma of the fundic-gland type (GAFG) and explore the possible mechanism of tumor development. Samples from 10 Chinese patients with GAFG were collected at the Peking University International Hospital and Liaocheng People's Hospital between January 2015 and March 2022. The nucleic acid sequence of Epstein Barr virus-encoded RNA (EBV-EBER) was detected by in situ hybridization. Genetic mutation information for GNAS, KRAS, NRAS, BRAF, PIK3CA, TP53, APC, CTNNB1, HER2, MLH1, MSH2, MSH6, and PMS2 was obtained by Next-Generation Sequencing, and the relevant literature was reviewed. A total of eight instances of missense mutations were detected, consisting of seven cases with GNAS mutations, two cases with KRAS mutations, and one case with a TP53 mutation. Additionally, two patients had simultaneous missense mutations in GNAS and KRAS. Nonsynonymous mutations in APC, CTNNB1, NRAS, BRAF, PIK3CA, HER2, MLH1, MSH2, MSH6, or PMS2 were not observed in any cases. In addition, all tumors were EBER-negative. GAFG exhibits diversity at the molecular level, and GNAS mutations are more common than KRAS mutations, TP53 mutations, and microsatellite instability. To date, no association between EBV/HER2 and GAFG has been found.