Relationship between genetic abnormalities of cell cycle regulators and genetic and chromosomal instabilities in gastrointestinal carcinomas

1.胃肠道肿瘤的遗传和染色体不稳定性用微卫星分析检测了胃癌的遗传不稳定性(复制误差：PER)，发现30%的病例存在遗传不稳定性。尤其是D17S855基因座(BRCA1附近)的不稳定性在年轻患者中更为常见。癌旁肠上皮化生组织中也可检测到RER。3%的胃癌组织中存在两个以上的端粒酶活性，其中半数为多原发癌。大多数胃癌组织和部分癌前病变组织端粒酶活性较强，hTR基因表达增强。大多数胃癌和结直肠癌端粒酶活性与TERT表达水平呈正相关。部分胃腺瘤和肠化生组织中也检测到TERT的表达。胃肠道癌基因扩增和o…中细胞周期调节因子的遗传异常Cyclin E在胃癌和结直肠癌中的高表达与高度恶性程度密切相关。约70%的胃癌高表达CDC25B。CDK抑制因子p27的低表达与胃癌和结直肠癌的侵袭行为(晚期、深度侵袭和淋巴结转移)密切相关。E2F-1是细胞周期调控的重要靶分子，在4%的胃癌和25%的结直肠癌中检测到基因扩增。约40%的胃癌组织中E2F-1基因过表达，而70%的胃癌组织中E2F-3基因表达下调。端粒酶与细胞周期调控因子的关系胃癌组织中端粒酶活性与多种细胞周期蛋白和CDK抑制剂表达的关系细胞周期蛋白E的表达与端粒酶活性呈正相关，而与p21、p27的表达无明显相关性。较少

1. Genetic and chromosomal instabilities in gastrointestinal carcinomasGenetic instability (replication error : PER) was examined in the gastric carcinomas by microsatellite analysis, and was found in 30% of the cases. Especially, the instability at D 17S855 locus (near BRCA1) was frequent in younger patients. RER was also detected in a part of intestinal metaplasia next to gastric carcinoma. RER at more than two of the four loci was found in 3% of the gastric carcinomas, a half of which had multiple primary cancers.Strong telomerase activity and increased hTR expression were detected in most of the gastric carcinomas and a portion of precancerous lesions. The telomerase activities were well correlated with the levels of TERT expression in most of the gastric and colorectal carcinomas. TERT expression was also detected in some of the adenomas and intestinal metaplasia of the stomach.2. Genetic abnormalities of cell cycle regulators in gastrointestinal carcinomasGene amplification and o … More verexpression of cyclin E occurred frequently in the gastric and colorectal carcinomas that was closely related with high grade malignancy. About 70% of the gastric carcinomas expressed CDC25B at high levels. Reduced expression of p27, a CDK inhibitor, correlated well with aggressive behavior (advanced tumor stage, deeply invasion, and lymph-node metastasis) of the gastric and colorectal carcinomas. Gene amplification of E2F-1, an important target molecule of cell cycle regulators, was detected in 4% and 25% of the gastric and colorectal carcinomas, respectively. About 40% of the gastric carcinomas overexpressed E2F-1 mRNA.On the other hand, the expression of E2F-3 was reduced in 70% of the gastric carcinomas.3. Relationship between telomerase and cell cycle regulatorsRelationship between telomerase activity and the expression of various cyclins and CDK inhibitors in the gastric carcinomas. The expression of cyclin E tended to correlate with the telomerase activity, while no obvious tendency was detected between telomerase and the expression of p21 and p27. Less