AI Article Synopsis
- The recent decline in Helicobacter pylori infections has coincided with an increase in foveolar-type gastric adenoma (FGA) cases in H. pylori-naive individuals, indicating a shift in the characteristics of gastric tumors.
- The study analyzed genomic features of sporadic FGA by performing whole genome sequencing on fresh-frozen tissue samples and examining cell proliferation and apoptosis profiles.
- Notably, researchers identified a common single-nucleotide variation (SNV) in the tumor suppressor gene KLF4, which seems to impede cell growth, suggesting that this genetic change may contribute to the slow-growing nature of sporadic FGA.
Article Abstract
Along with a recent remarkable decrease in Helicobacter pylori-infected individuals, reports of gastric neoplasms such as sporadic foveolar-type gastric adenoma (FGA) in H. pylori-naive patients have been increasing. This tumor, with its raspberry-like appearance, is common in H. pylori-naive gastric mucosa. The current study investigated the genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori-naive patients were subjected to whole genome analysis using a next-generation sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial cells, along with plasmid transfection of candidate variants, were examined. A mean of 6.65 × 10 total reads were obtained for each sample. Common genetic abnormalities in well-known proliferation driver genes of conventional gastric dysplasia/cancer were not found. However, a common single-nucleotide variation (SNV) was noted within the DNA-binding domain of the tumor suppressor gene KLF4. This novel SNV was located in the zinc finger 2 region. Additional experiments showed that it significantly suppressed proliferation of gastric epithelial cells compared with wild-type KLF4 plasmid-transfected cells, although suppression was reduced in early apoptotic phase-related genes. A novel SNV in the KLF4 zinc finger 2 region was commonly found in sporadic FGA tissue samples, which may explain the slow-growing properties of this neoplasm.
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| http://dx.doi.org/10.1016/j.ajpath.2022.06.005 | DOI Listing |
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