Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun'yahabachou, 028-3695, Japan.
Diagnostic Pathology Center, Southern Tohoku General Hospital, 7-115, Yatsuyamada, Kooriyama City, Fukushima, 963-8563, Japan.
Gastric Cancer. 2024 Nov;27(6):1220-1228. doi: 10.1007/s10120-024-01543-0. Epub 2024 Aug 12.
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.
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.
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.
The current molecular profiles of IFN may help elucidate the mechanisms of IFN development.
胃窝型肿瘤是胃肿瘤的一种罕见组织学变异型。良性和恶性上皮内窝状肿瘤（IFN）之间的鉴别非常困难。虽然 IFN 中已经确定了有限的分子改变，但与肿瘤进展相关的体细胞拷贝数改变（SCNAs）尚未在 IFN 中进行系统评估。
本研究旨在使用 SNP 阵列全面检查 37 例 IFN 中的 SCNAs，与肠型异型增生进行比较，包括 39 例低级别异型增生（LGD）和 32 例高级别异型增生（HGD）。此外，使用基因panel 评估基因突变。最后，我们尝试使用层次聚类分析确定分子谱。
根据 108 个肿瘤的 SCNAs 可分为两种模式：高（亚组 1）和低（亚组 2）SCNAs 频率。虽然 IFN 和 LGD 与亚组 2 相关，但 HGD 存在于两个亚组中。IFN 或 HGD 中的总 SCNAs 和拷贝数增益中位数高于 LGD。此外，IFN 基因型的特征是位于 4p13-4q35.2 的改变基因，包括 RAP1GDS1 和 LEF1，这可能与 IFN 的发展有关。最后，使用基因 panel 未发现 IFN 中的显著突变。
IFN 的当前分子谱可能有助于阐明 IFN 发展的机制。
