| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
To know the chromosomal changes that are important in progerssion of gastrointestinal cancers, we tried comparative genomic hybridization (CGH) on a cell line and frozen primary tumors. Using a gastric cancer cell line (MKN-7), we compared the copy number of chromosome/chromosomal locus that were inferred from the CGH profilie and ploidy data and actual copy number determined by fluresoence in situ hybridization (FISH) with centromeric and locus-sperific DNA probes. We obtained a concordant results between the inferred and actual copy numbers of the chromosomes that showed minimal heterogeneity in copy number.
To differentiate the nonspecific numerical chromosomal changes associated with genome duplication from those specific to tumor development, we confined our material of the primary tumor to DNA-diploid, intramucosal signet ring cell carcinomas of the stomach. We extracted DNA for CGH from freshly frozen intramucosal tumor part after enrichment of tumor cells by microdissection. The process of enrichment of tumor cells plays a crucial role in obtaining reliable CGH data, and there is still room for improvement in the process. We used the profile of CGH of the normal-normal DNA combination as the control. Though, at present, we have not get the data of enough cases, our preliminary results showed that chromosomal changes were less in degree than expected in this type of carcinoma. a few candidate loci remained possible as the common chromosomal changes in this carcinoma.
As to colorectal cancers, we confirmed the importance of chromosomes 7 and 18 as earlier changes. We compared the ploidy and copy number of these chromosomes and revealed frequent presence of trisomy 7 and monosomy 18 in DNA-diploid tumor components. As in DNA-aneuploid component, duplication of the aberration was common, DNA-aneuploid component was inferred to emerge through genome duplication from DNA-diploid component.
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