Genetic alterations in cancers of digestive tract as analyzed by CGH, in relation to genesis of cancer and the metastasis.

从1994年到1997年，我们通过比较基因组杂交（Comparative Genomic Hybridization， CGH）分析了切除的胃癌样本的DNA拷贝数变化，发现变异模式的差异取决于分化程度和肿瘤分期（Clinical cancer Research 3: 1067-1076, 1997）。在这项研究中，我们通过在根除幽门螺杆菌之前和之后检查低级别MALToma组织进一步扩展了这些发现。从内窥镜和组织学观察来看，根除导致MALToma完全或部分消退。为了了解这种“回归”是否也发生在DNA水平上，对样品进行了CGH分析。我们发现了DNA异常仍然保留的病例，尽管在根除后被判断为正常。我们也在分析结肠癌、胃癌和肝细胞癌的癌前病变，以发现肿瘤发生初期的遗传改变。为了评估在胃癌中获得的发现，我们还分析了肾上腺皮质肿瘤中与恶性程度和激素产生有关的遗传改变，根据这些遗传改变，我们发现了CGH改变模式的差异。最后，我们检查了口腔鳞状细胞癌的遗传改变，发现1q、3q、5q、8q、11p、11q、13q和20p基因扩增，而18q基因的DNA拷贝数减少。

From 1994 to 1997, we analyzed resected gastric cancer samples for the DNA copy number alterations by CGH (Comparative Genomic Hybridization) and found differences in pattern of alterations depending on the extent of differentiation and tumor stage (Clinical Cancer Research 3 : 1067-1076, 1997). In this research, we have further extended these findings by examining low grade MALToma tissues before and after eradication of H. pylori. The eradication resulted in complete or partial regression of MALToma judging from endoscopic and histological observations. To see whether this "regression " also occurred at DNA level, the samples were subjected to CGH analysis. We found cases where DNA abnormality was still retained, though judged to be normal after the eradication. We are also analyzing precancerous lesions of colon and gastric, and hepatocellular carcinomas to find genetic alterations at initial stages of tumorigenesis.To evaluate the findings obtained in gastric cancers we also analyzed adrenocortical tumors for genetic alterations in relation to extent of malignancy and homone production, depending on which we found differences in alteration patterns by CGH. Finally, we have examined genetic alsterations in oral squamous cell carcinomas and found amplifications in 1q, 3q, 5q, 8q, 11p, 11q, 13q, and 20p while decrease of DNA copy number in 18q.