|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1997 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Gene abnormalities of initial-stage carcinomas of diffuse-type in the stomach, in particular of signet-ring cell type, remain unknown. We have previously proved by cytofluorometry that diffuse-type carcinomas mainly show diploid pattern in the early stage but most of them in the advanced stage show aneuploid pattern ; suggesting that aneuploid cells occur with tumor progression.
In 1996, microsatellites instability (MSI) and loss of heterozygosity (LOH) in 10 loci of microsatellites were analyzed in signet-ring cell carcinomas in the early and advanced stage. MSI,and LOH at the microsatellite linked to the gene associated with cell adhesion molecules were found in some signet-ring cell carcinomas in the early stage.
In 1997, all chromosomal abnormalities were screened in signet-ring cell carcinomas by comparative genomic hybridization (CGH). While no abnormality was found in tumors in the early stage, gain of copy numbers at the chromosome 7 was observed in some advanced tumors. We also analyzed multiple areas of superficially spreading type carcinomas including signet-ring cells by a clonarity assay based on inactivation of X chromosome, and most of them were proved to be monoclonal origin.
In summary, most of diffuse-type carcinomas in the initial stage are diploid only with MSI and abnormalities of cell adhesion molecules, which monoclonally and surerficially spread in the mucosa. With tumor progression to the advanced stage, aneuploid cells may occur associated with abnormalities in an unknown gene at the chromosome 7.