|Budget Amount *help
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2000: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥6,500,000 (Direct Cost: ¥6,500,000)
We aimed to identify tumor suppressor genes involved in multi-step gastrointestinal carcinogenesis through genome-wide scanning of alteration in either DNA or RNA levels in tumor. First, Representational Difference Analysis (RDA) was applied to identify homozygously deleted chromosomal regions in tumor cells, which could be putative tumor suppressor loci. In the stomach cancer cell line OCUM-2MD3, prone to peritoneal dissemination, three chromosomal loci, 1p, 3pl4 and 16q22, were found to be homozygously deleted. Putative tumor suppressor genes, FHJT and WWOX, are located in the 3p and 16q deletion, respectively, while a novel gene, ZAP1, was isolated from 1p deletion, and its aberrant transcripts were found in various cancer cell lines. Secondly, DNA chip analysis was performed to monitor altered expression profiles of thousands of genes. In 2MD3 cell, genes specific for squamous cell lineage were up-regulated, while MHC class II genes were up-regulated in 2MLN cell line. In primary gastric cancers genes discriminating between cancer and non-cancer, or between metastasis (+) and (-) have been identified. Genes involved in de-differentiation of liver tumors were also obtained and utilized to classify differentiation grades of liver cancers. Nonparametric statistical analysis, like Kruskal-Wallis test, and non-hierarchial clustering were also very useful in molecular classification of cancer.