Differences in Somatic Mutation Profiles between Korean Gastric Cancer and Gastric Adenoma Patients

Background: We aimed to investigate molecular factors potentially related to the progression of gastric adenoma (GA) to gastric cancer (GC) and compare the mutation characteristics between GC and GA. Methods: We conducted custom gene panel sequencing for 135 GC-related genes and estimated the difference in somatic mutation profiles between 20 GC and 20 GA cases. Results: A total of 31 somatic mutations, including 22 missense, 3 nonsense, and 6 frameshift mutations, were detected in 17 samples. We estimated an average of 1.8 mutations per sample (range, 1 to 3 mutations), with 12 in GC and 5 in GA. GC tended to have one or more mutated genes (p = 0.0217), as well as higher allele frequencies of mutated genes (p = 0.0003), compared to GA. Likewise, known driver mutations associated with GC tumorigenesis (TP53, ERBB2, PIK3CA, and RNF43) were identified in half of the GC cases (50%, 10/20; p = 0.0002). Only the mutant burden, regardless of gene type, was retained, with an odds ratio of 1.8392 (95% confidence interval (CI), 1.0071 to 3.3588; p = 0.0474). Conclusion: Our study demonstrates that the accumulation of mutant burden contributes to tumorigenesis progression from GA to GC in Korean patients, regardless of the kind of genes. These findings may elucidate the molecular pathogenesis of gastric carcinogenesis and malignant progression.

Automated summary

The study found differences in mutation profiles between GC and GA, with GC cases having more mutated genes and higher allele frequencies. Common driver mutations were more prevalent in GC cases as well. The accumulation of mutant burden was shown to contribute to the progression from GA to GC, regardless of gene type. Overall, these findings are important in elucidating the molecular pathogenesis of gastric cancer.