Mori Y, Matsunaga M, Abe T, Fukushige S, Miura K, Sunamura M, Shiiba K, Sato M, Nukiwa T, Horii A
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Br J Cancer. 1999 May;80(3-4):556-62. doi: 10.1038/sj.bjc.6690391.
We have analysed the loss of heterozygosity (LOH) on chromosome bands 16q22-q24 in 24 primary gastric cancer tissues and found three regions of frequent allelic loss (16q22, 16q24.1-q24.3 and 16q24.3). The region for the most frequent allelic loss (63%) was in 16q24.1-q24.3. LOH of this region had no relationship with histological subtype, but a significant association between LOH and microscopic lymphangial invasion was observed. Although not significant, vascular and gastric wall invasions are also associated with LOH. The region includes the locus for the H-cadherin gene. Therefore we examined the genetic and epigenetic alterations of this gene. Markedly reduced expression was observed in gastric cancer cell lines compared with that of normal gastric mucosa. However, no mutation was found in this gene in any of the gastric cancer tissues or the gastric cancer cell lines. Furthermore, we analysed the methylation status of the 5'-flanking region of the gene, but no significant association was found. We suggest that some other tumour suppressor gene(s) in 16q24.1-q24.3 may be responsible for gastric carcinogenesis.
我们分析了24例原发性胃癌组织中16q22 - q24染色体带的杂合性缺失(LOH),发现了三个常见等位基因缺失区域(16q22、16q24.1 - q24.3和16q24.3)。最常见等位基因缺失区域(63%)位于16q24.1 - q24.3。该区域的LOH与组织学亚型无关,但观察到LOH与微小淋巴管浸润之间存在显著关联。虽然不显著,但血管浸润和胃壁浸润也与LOH有关。该区域包含H - 钙黏蛋白基因的位点。因此,我们检测了该基因的遗传和表观遗传改变。与正常胃黏膜相比,在胃癌细胞系中观察到该基因表达明显降低。然而,在任何胃癌组织或胃癌细胞系中均未发现该基因的突变。此外,我们分析了该基因5' - 侧翼区域的甲基化状态,但未发现显著关联。我们认为16q24.1 - q24.3中的某些其他肿瘤抑制基因可能与胃癌发生有关。