贲门癌中染色体8p21-p23杂合性丢失的研究

Loss of Heterozygosity at Chromosome 8p21-p23 in Adenocarcinoma of Gastric Cardia

染色体Sp21-p23区域存在与多种肿瘤相关的抑癌基因。为明确该染色体区域的抑癌基因与贲门癌的关系，我们进行了贲门癌中染色体8p21-p23区域微卫星标记的杂合性丢失研究。首先采用激光捕获显微切割技术从19例贲门癌组织中获得均质的肿瘤细胞及正常的胃粘膜细胞，然后利用多重置换扩增技术扩增捕获细胞的全基因组DNA。选择覆盖染色体8p21-p23区域的13个微卫星标记，利用PCR结合硝酸银染色方法分析了肿瘤细胞中染色体8p21-p23的杂合性丢失情况。结果显示，在贲门癌中染色体8p21-p23的总丢失频率高达63．2％（12／19），单一标记的丢失频率为25％～55．6％。根据不同肿瘤组织中杂合性丢失的情况，我们确定了一个最小缺失区域，即8p22GGAA-8p22ATCT标记间约1．2Mb的范围。研究结果表明，染色体8p22区域抑癌基因在贲门癌发生发展中起重要作用；染色体最小重叠区域的确定对最终鉴定该区域内的抑癌基因有参考价值。

Chromosome 8p21-p23 harbors tumor suppressor gene（s） implicated in multiple types of cancers. To inves tigate the involvement of the gene（s） in the carcinogenesis of adenocarcinoma of gastric cardia, loss of heterozygosity （LOH） for microsatellite markers at chromosome 8p21-p23 was examined. Laser capture microdissection （LCM） was used to obtain homogeneous tumor cells from 19 surgical specimens. Subsequently, genomic DNA extracted from the LCM-captured cells was amplified by multiple displacement amplification. Each tumor was assessed for allelic loss u- sing 13 microsatellite markers. An overall LOH frequency of 63.2 % （12/19） was observed and the LOH frequency for individual markers varied from 25 % to 55.6 %. One common deleted region of about 1.2 Mb （8p22GGAA-8p22ATCT） was defined. Our data indicated that the tumor suppressor gene at chromosome 8p22 might play an important role in the development of adenocarcinoma of gastric cardia.