Along with a recent remarkable decrease in Helicobacter pylori–infected individuals, reports of gastric neoplasms in H. pylori–naive patients have been increasing. A sporadic foveolar-type gastric adenoma (FGA)
is one such type, and we recently reported that occurrence of this tumor is not rare
in H. pylori–naive gastric mucosa and its raspberry-like appearance. This study investigated the
genomic features of sporadic FGA. Fresh-frozen sporadic FGA tissue samples from H. pylori–naive patients underwent whole genome analysis performed using a next-generation
sequencer. Proliferation ability and apoptotic profiles of human gastric epithelial
cells, along with plasmid transfection of candidate variants, were then examined.
A mean of 6.65 × 108 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, and additional experiments
showed that it significantly suppressed proliferation of gastric epithelial cells
compared with wild-type KLF4 plasmid transfection 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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Article Info
Publication History
Published online: June 21, 2022
Accepted:
June 8,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Supported in part by Ministry of Education, Science, Sport, and Culture of Japan grant 19K23945 .
Identification
Copyright
© 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
