Tamura G, Sakata K, Nishizuka S, Maesawa C, Suzuki Y, Terashima M, Eda Y, Satodate R
Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
J Pathol. 1996 Dec;180(4):371-7. doi: 10.1002/(SICI)1096-9896(199612)180:4<371::AID-PATH704>3.0.CO;2-2.
The molecular mechanism of gastric tumourigenesis has not yet been clarified, although investigators have postulated that differentiated adenocarcinoma may arise from pre-existing adenoma, similarly to the colorectal adenoma-carcinoma sequence. An allelotype analysis has been performed to identify chromosomal regions which are frequently deleted in gastric tumours and to examine the significance of the adenoma-carcinoma sequence in gastric tumourigenesis. Forty-five gastric tumours, 20 adenomas, and 25 differentiated adenocarcinomas were examined for loss of heterozygosity (LOH) using 39 microsatellite markers covering each non-acrocentric chromosome arm. Frequent LOH in the adenocarcinomas was observed on chromosomes 2q (33 per cent), 4p (33 per cent), 5q (50 per cent), 6p (33 per cent), 7q (43 per cent), 11q (36 per cent), 14q (38 per cent), 17p (45 per cent), 18q (36 per cent), and 21q (40 per cent). In contrast, the incidence of LOH in adenomas did not exceed 10 per cent at any of the loci examined. In addition to the p53 gene on 17p and the DCC gene on 18q, which are known to be frequently deleted in differentiated adenocarcinomas of the stomach, other unknown tumour suppressor genes on the above-mentioned chromosomes may also be inactivated. These observations suggest that the adenoma-carcinoma sequence is not a major pathway in gastric tumourigenesis.
尽管研究人员推测,与结直肠腺瘤-癌序列相似,分化型腺癌可能起源于已存在的腺瘤,但胃癌发生的分子机制尚未阐明。已进行等位基因分型分析,以确定在胃肿瘤中经常缺失的染色体区域,并研究腺瘤-癌序列在胃癌发生中的意义。使用覆盖每个非近端着丝粒染色体臂的39个微卫星标记,对45例胃肿瘤、20例腺瘤和25例分化型腺癌进行杂合性缺失(LOH)检测。在腺癌中,观察到2q(33%)、4p(33%)、5q(50%)、6p(33%)、7q(43%)、11q(36%)、14q(38%)、17p(45%)、18q(36%)和21q(40%)染色体上频繁出现LOH。相比之下,在所检测的任何位点,腺瘤中LOH的发生率均不超过10%。除了已知在胃分化型腺癌中经常缺失的17p上的p53基因和18q上的DCC基因外,上述染色体上的其他未知肿瘤抑制基因也可能失活。这些观察结果表明,腺瘤-癌序列不是胃癌发生的主要途径。