Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Med Genet. 2020 Jun;57(6):385-388. doi: 10.1136/jmedgenet-2018-105752. Epub 2019 Mar 15.
Spasmolytic polypeptide-expressing metaplasia (SPEM) is present in more than 90% of resected gastric cancer tissues. However, although widely regarded as a pre-cancerous tissue, its genetic characteristics have not been well studied.
Immunohistochemistry using Trefoil factor 2 (TFF2) antibodies was used to identify TFF2-positive SPEM cells within SPEM glands in the stomach of -infected mice and human clinical samples. Laser microdissection was used to isolate specific cells from both the infected mice and the human samples. The genetic instability in these cells was examined by measuring the lengths of microsatellite (MS) markers using capillary electrophoresis. Also, genome-wide genetic variations in the SPEM cells from the clinical sample was examined using deep whole-exome sequencing.
SPEM cells indeed exhibit not only heightened MS instability (MSI), but also genetic instabilities that extend genome-wide. Furthermore, surprisingly, we found that morphologically normal, TFF2-negative cells also contain a comparable degree of genomic instabilities as the co-resident SPEM cells within the SPEM glands.
These results, for the first time, clearly establish elevated genetic instability as a critical property of SPEM glands, which may provide a greater possibility for malignant clone selection. More importantly, these results indicate that SPEM cells may not be the sole origin of carcinogenesis in the stomach and strongly suggest the common progenitor of these cells, the stem cells, as the source of these genetic instabilities, and thus, potential key players in carcinogenesis.
舒血管肠肽表达化生（SPEM）存在于超过 90%的胃癌切除组织中。然而，尽管它被广泛认为是一种癌前组织，但它的遗传特征尚未得到很好的研究。
使用三叶因子 2（TFF2）抗体的免疫组织化学方法鉴定感染小鼠和人类临床样本胃中 TFF2 阳性 SPEM 腺内的 TFF2 阳性 SPEM 细胞。使用激光微切割从感染小鼠和人类样本中分离特定的细胞。通过使用毛细管电泳测量微卫星（MS）标记物的长度来检查这些细胞中的遗传不稳定性。此外，使用深度全外显子组测序检查临床样本中 SPEM 细胞的全基因组遗传变异。
SPEM 细胞不仅表现出更高的 MS 不稳定性（MSI），而且还表现出扩展到全基因组的遗传不稳定性。此外，令人惊讶的是，我们发现形态正常、TFF2 阴性的细胞也含有与 SPEM 腺内共驻的 SPEM 细胞相当程度的基因组不稳定性。
这些结果首次明确确立了升高的遗传不稳定性是 SPEM 腺的一个关键特性，这可能为恶性克隆选择提供了更大的可能性。更重要的是，这些结果表明 SPEM 细胞可能不是胃发生癌变的唯一起源，强烈提示这些细胞的共同祖细胞，即干细胞，是这些遗传不稳定性的来源，因此是癌变的潜在关键因素。
