胃癌细胞系和胃癌组织中线粒体DNA 4977 bp缺失及其生物学意义  

Frequent 4977 bp deletion of mitochondrial DNA in tumor cell lines, solid tumors and precancerous lesions of human stomach

作　　者：沈慧[1] 赵敏[1] 董彬[1] 唐巍[2] 肖白[3] 刘敬忠[3] 吕有勇[1] 

机构地区：[1]北京大学临床肿瘤学院北京市肿瘤防治研究所,10034 [2]北京大学临床肿瘤学院病理科 [3]北京市红十字朝阳医院

出　　处：《中华医学杂志》2003年第17期1484-1489,共6页National Medical Journal of China

基　　金：国家重点基础研究发展规划肿瘤项目(980 3 12 0 0 );北京基因诊断实验室资助项目(JS960 0 4);北京大学985资助项目

摘　　要：目的　明确线粒体DNA 4 977bp大片段缺失在胃癌细胞系、胃癌组织及胃癌患者血清中的频率 ,为胃癌的早期临床诊断寻找简便准确的分子标记。方法　运用Primer shiftPCR和直接测序的方法对 13个胃癌细胞系、5 2对胃癌组织及对应的癌旁正常组织 (年龄从 2 8～ 78岁 )、4 0例胃癌患者血清及 4 0名正常人血清进行筛查。取 10例胃癌组织的石蜡切片 ,采用显微切割技术在同一患者的切片上同时分离 3种组织 (包括胃粘膜正常腺体、肠化上皮及胃癌组织 )对mtDNA 4 977bp缺失进行了分析比较。结果　在 13个胃癌细胞系中 12个有mtDNA 4 977bp缺失 (缺失率为 92 3% ) ,5 2例胃癌组织中 38例有缺失 (缺失率为 73 1% ) ,5 2例癌旁正常组织中 2 7例有缺失 (缺失率为 5 2 % ) ,4 0名胃癌患者血清中 17例有缺失 (缺失率为 4 2 5 % ) ,4 0名正常人血清中 8例有缺失 (缺失率为2 0 % )。胃癌组织和癌旁正常组织mtDNA 4 977bp缺失差异有显著意义 ,癌组织mtDNA4 977bp缺失率与胃癌的分型和患者的性别没有关联。胃癌患者血清与正常人血清mtDNA 4 977bp缺失差异也有显著意义。 10例显微切割组织中 2例肠化上皮及胃癌组织中有缺失 ,而胃粘膜正常腺体未见缺失。结论　线粒体DNA 4 977bp大片段缺失可能在胃癌发生和胃粘膜病变演化及?Objective To clarify the frequence of mtDNA 4 977 bp deletion in tumor cell lines? solid tumors? patient′s serum of gastric tumor and to find a easy and exact method to diagnose gastric tumor Methods Primer shift PCR method was used in 13 gastric tumor cell lines?52 cases of gastric fresh tumor tissues matched the adjacent normal tissues?40 cases of patient's serum of gastric tumor and 40 cases of normal serums for analysis of mtDNA deletion Results Frequence of 4 977 bp mtDNA deletion was detected in 12 of 13(92 3%) tumor cell lines?38 of 52(73 1%) cases of solid tumor tissues?27 of 52(52%) adjacent normal tissues?17 of 40(42 5%) patient's serum and 8 of 40(20%) normal serums Further more,in 2 of 10 pairs microdissected specimens,we found this deletion occured not only in primary tumor but also in intestinal metaplasia comparing with no deletion was found in normal tissues The frequence of this deletion was statistically significantly higher in the gastric tumor tissues and serums than in the adjacent normal tissues and serums A good correlation between the deletion and young age of patients was reprent in our data Conclusion mtDNA 4 977 bp deletion maybe play an important role in the carcinogenesis of human gastric mucous and maybe has happened in the tumor cell maligment transformation To detect this deletion in patient′s serum is a easy and exact method and maybe become a potential tumor marker

关 键 词：胃癌细胞系 胃癌组织 线粒体 DNA4977bp缺失 

分 类 号：R735.2[医药卫生—肿瘤]