摘要
目的探讨胃癌5号染色体短臂（5p）微卫星标记杂合性缺失（LOH）与胃癌组织学表型的相关性。方法收集80例手术切除的胃癌标本及其配对正常胃黏膜组织。部分标本抽提基因组DNA，选用分布于5号染色体短臂上17个微卫星多态标记进行LOH分析；部分标本以10％中性福尔马林固定，石蜡包埋，进行常规切片染色，采用Lauren分型法进行组织病理学分型。结果5号染色体短臂17个微卫星标记的平均信息性病例比例为60．0％（48／80），35．0％（28／80）的病例至少一个位点检测到LOH。D5S2849位点（7．77eM）LOH频率最高，为35．2％（19／54）。5p最小丢失区域在6．67～9．41eM区间（涵盖2．7eM，1．18Mb），定位为5p15．33区，包括D5S417、D5S2849、D5S1492和D5S2088位点。28例携带LOH的病例中，24例（85．7％）为肠型胃癌，4例（14．3％）为弥漫型胃癌，肠型胃癌的LOH频率显著高于弥漫型胃癌病例（P〈0．01）。NCBI基因数据库检索显示，该区内含有IRX1、IRX2和CEI3个基因。结论5p15．33区发生的分子遗传学改变可能参与胃癌的形态分化和发展，使胃癌分化成肠型与弥漫型不同的组织学类型。5p15．33最小丢失区内的基因簇可能与胃癌，尤其是肠型胃癌的发生发展相关。
Objective To explore the relationship between loss of heterozygosity （LOH） of 5p with the histological phenotype in gastric cancer. Methods Eighty pairs of tumor and adjacent normal mucosa samples were collected and genomic DNA was extracted. Total of 17 polymorphic microsatellite markers for 5p were used for LOH analysis. A part of samples were fixed in 10% buffered formalin and stained with H＆E. Histological type of gastric cancer was defined according to Lauren＇s classification. Results The average informative rate of all seventeen markers was 60.0%. The LOH at least in one locus was detected in 28 of the 80 （35.0%） cases. The highest LOH frequency occurring at D5S2849 （7.77 cM）, with LOH frequency of 35.2% （19/54）. The minimal LOH region was spanned from 6.67 to 9.41 cM （1.18 Mb, covering 2.7 cM）, including D5S417, D5S2849, D5S1492 and D5S2088. In 28 with LOH, 24 （85.7%） cases were of intestinal type, and only 4 cases （ 14.3% ） were of diffuse type. There is significant difference between LOH frequency in intestinal-type and diffuse-type gastric cancers （ P 〈0.01 ）. Searching the NCBI database disclosed that this minimal deletion region at 5p15.33 covered 3 candidate genes, IRX1, IRX2, and CEI. Conclusion The molecular events in 5p 15. 33 may be related with the morphological differentiation and development of gastric cancer. Gastric cancer with LOH of 5p 15.33 locus tends to develop in to intestinal type. The cluster of candidate genes in 5p15.33 may be closely implicated in carcinogenesis of intestinal type gastric carcinoma.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2006年第2期84-87,共4页
Chinese Journal of Oncology
基金
科技部国家高技术研究发展计划资助项目(2002BA711A06)
国家自然科学基金资助项目(30572127)
上海市科委重点基础研究项目(05JC14013)
上海交通大学医学院自然科学研究基金资助项目(04JXJ21021)
关键词
胃癌
5号染色体
相关基因
Gastric cancer
Chromosome 5
Candidate genes
