The molecular profile of gastric intraepithelial foveolar type neoplasia based on somatic copy number alterations and multiple mutation analysis

Gastric Cancer. 2024 Nov;27(6):1220-1228. doi: 10.1007/s10120-024-01543-0. Epub 2024 Aug 12.

Abstract

Background: Gastric foveolar type neoplasia is a rare histological variant of gastric tumors. It is very difficult to differentiate between benign and malignant intraepithelial foveolar neoplasia (IFN). Although limited molecular alterations have been identified in IFNs, somatic copy number alterations (SCNAs), which are linked to tumor progression, have not been systematically evaluated in IFN.

Methods: The aim of the present study was to comprehensively examine SCNAs using a SNP array in 37 cases of IFN, compared with intestinal type dysplasia, including 39 low grade (LGD) and 32 high grade dysplasia (HGD) cases. In addition, gene mutations were evaluated using a gene panel. Finally, we attempted to determine molecular profiles using a hierarchical clustering analysis.

Results: Two patterns could be categorized according to the SCNAs in 108 tumors examined: high (subgroup 1) and low (subgroup 2) frequencies of SCNAs. Although IFN and LGD were associated with subgroup 2, HGD was found in both subgroups. The median numbers of total SCNAs and copy number gains were higher in IFN or HGD than in LGD. In addition, the IFN genotype was characterized by altered genes located at 4p13-4q35.2, including RAP1GDS1 and LEF1, which may be associated with IFN development. Finally, no significant mutations were found in IFNs using a gene panel.

Conclusions: The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.

Keywords: Foveolar type neoplasia; Gastric cancer; Molecular profile; Mutation; Somatic copy number alteration.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / pathology
  • DNA Copy Number Variations*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology