摘要
为进一步明确胃粘膜癌变过程中基因变异的规律，本研究以胃癌手术标本、胃镜活检标本、体外培养细胞为研究体系，利用聚合酶链反应／限制性内切酶长度多态性（ＰＣＲ／ＲＦＬＰ）、ＰＣＲ／单链构象多态性（ＳＳＣＰ）、ＤＮＡ序列分析、免疫组化及原位杂交多项研究手段，系统研究了６０例胃癌、３０例异型增生和３３例肠上皮化生病变中基因的改变。确定胃癌中存在着多种基因结构及表达的异常，主要表现为Ｈ－ｒａｓ低甲基化、过量表达，ｍｅｔ、ｅｒｂＢ２、ＥＧＦＲ、ａｋｔ２基因扩增。ＡＰＣ、ｐ１６基因缺失和ｐ５３基因点突变，其中ｐ５３基因点突变的频率为５８％，异型增生为２０％，肠上皮化生为６％。突变多发生在第１４３、１７４、１７５、２２３、２４５和２８０位，其中第１７４和２８０位的突变在胃癌实体瘤和培养细胞中都检测到。免疫组化显示ｐ５３染色阳性为５４％，与ＳＳＣＰ得到的结果相似。用染色体原位杂交和Ｎｏｒｔｈｏｒｎ杂交分析发现，ｐ５３基因缺失、低表达在胃癌细胞中也较普遍。显示在恶性度较高的病例中有多个基因的变异，其中在ｐ５３基因有异常的肿瘤多表现为低分化和高转移率，而且病人术后生存期明显低于ｐ５３基因未突变组。这一结果提示ｐ５３基因异常与胃癌的?
The investigation of molecular evidence of gastric carcinoma will be contributable to the prevention,gene diagnosis and therapy of human gastric neoplasms.To determine the specific genetic change in human gastric cancer(HGC) and precancerous lesions,we analysized FISH,PCR/SSCP,IHC and DNA sequencing by using multiple probes to detect the gene abnormalities (mutation,deletion,amplification or overexpression of genes)of 67 fresh tumors,63 endoscopic biopies including 30 dysplasia(DYS)and 33 intestinal metaplasia(IM,and 4 tumor cell lines from HGC patients.Multiple genetic abnormalities including hypomethylation of H-ras gene,amplification and overexpression of met and erbB2,deletion of APC,mtsl/p16, p53 and nm23 gene and point mutation of p53 gene were noted in HGC and precancerous lesion of human gastric mucosa.Among these changes,p53 gene was the highest frequence genetic alteration in 39/67(54-58%)of gastric carcinoma.These results indicate that overexpression of met and H-ras occurs at early stage in progression of neoplasia,amplification of met,erbB2 and akt2 gene occurs at progressing stage of tumorigenesis,deletion of p53,APC,mtsl/p16 and nm23 occurs at advanced stage in the progression of cancer.The abno malities should be associated with malignant phenotytpes:poor differentiation,vascular invasion,lymph nodes metastasis,and low survival time.We detected p53 gene mutation in both cancer and precancerous lesions of IM and DYS.These results suggest that p53 may be a susceptible gene and alteration of p53 gene plays an important role in the development of HGC.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1995年第11期679-682,共4页
National Medical Journal of China
基金
国家863高科技发展计划基金
关键词
胃肿瘤
基因
P53
基因表达
基因突变
Stomach neoplasms Genes p53 Genes,structural, neoplasms Gene expression
