Abstract
Along with a recent remarkable decrease in Helicobacter pylori (Hp)-infected individuals, reports of gastric neoplasms in Hp-naïve 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 Hp-naïve gastric
mucosa and its raspberry-like appearance. This study was conducted to investigate
the genomic features of sporadic FGA.
Fresh-frozen sporadic FGA tissue samples from Hp-naïve 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.
An average 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 Krüppel-like factor 4 (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
as compared with wild-type-KLF4 plasmid transfection cells, though 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.
Keywords
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Article Info
Publication History
Accepted:
June 8,
2022
Received in revised form:
June 3,
2022
Received:
August 12,
2021
Publication stage
In Press Journal Pre-ProofFootnotes
Conflicts of interest: The authors have no financial conflicts of interest to declare.
Funding: This study was supported in part by a KAKENHI grant (No. 19K23945) from the Ministry of Education, Science, Sport, and Culture of Japan.
Identification
Copyright
© 2022 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.
