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Gene abnormalities in initial-stage carcinomas of diffuse type in the stomach.

胃弥漫型初期癌的基因异常。

基本信息

批准号：
08670245
负责人：
HATTORI Takanori
金额：
$ 1.28万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670245/
关键词：
stomach diffuse-type carcinoma signet-ring cell carcinoma microsatellite LOH CGH monoclonarity chromosome 胃癌 E-cadherin β-catenin DNA ploidy

项目摘要

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.

弥漫型胃癌，特别是印戒细胞型胃癌的基因异常尚不清楚。1996年我们对早期和晚期印戒细胞癌进行了微卫星不稳定性（MSI）和10个微卫星位点的杂合性丢失（洛）分析。在印戒细胞癌的早期发现了与细胞粘附分子相关的微卫星位点的MSI和洛，1997年，我们用比较基因组杂交（CGH）技术对印戒细胞癌进行了染色体异常筛查。虽然在早期肿瘤中未发现异常，但在一些晚期肿瘤中观察到7号染色体的拷贝数增加。我们还对包括印戒细胞在内的浅表扩散型癌的多个区域进行了基于X染色体失活的克隆性分析，证实大多数癌是单克隆起源的，总之，大多数弥漫型癌在初始阶段是二倍体，仅具有MSI和细胞粘附分子的异常，单克隆地在粘膜中表面扩散。随着肿瘤进展到晚期，非整倍体细胞可能与7号染色体上未知基因的异常相关。