Chung Y J, Choi J R, Park S W, Kim K M, Rhyu M G
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul.
Virchows Arch. 2001 Jan;438(1):31-8. doi: 10.1007/s004280000328.
To assess the extent and the timing of allelic loss required for the progression of gastric carcinoma, the intratumoral distribution of loss of heterozygosity (LOH) was compared in early and advanced tumors: early loss is uniformly observed in all tumor areas and late loss is localized in parts of tumor tissue. Tumor sites (167 sites) obtained from 42 gastric carcinoma tissues (26 advanced cancers and 16 early cancers) were examined for LOH on chromosomes 5q, 9p, 13q, 17p, and 18q. By using two or three microsatellite markers for each chromosome arm, it was shown that of 29 tumors showing LOH in at least one tumor site, 15 (51.7%, 12 advanced and three early cancers) harbored multiple losses on three or more chromosome arms, and 89.4% (84 of 94) of these losses was uniformly found in all tumor sites tested. In the remaining 14 tumors (48.3%, eight advanced and six early tumors) with sporadic losses on one or two chromosome arms, 44% (11 of 25) of the losses were commonly shared among the sites tested. Such marked difference (P<0.001, Fisher's exact test) in the intratumoral distribution of multiple and sporadic LOH patterns proposes two distinct LOH subtypes: multiple losses (high LOH), occurring at an early stage with a few additional losses, and sporadic losses (low LOH), taking place relatively late during tumor progression. The multifocal LOH findings imply that, rather than being gradual, the allelic losses take place in two manners that are already determined at an early stage.
为评估胃癌进展所需等位基因缺失的程度和时间，比较了早期和晚期肿瘤中杂合性缺失（LOH）的瘤内分布：早期缺失在所有肿瘤区域均一致观察到，而晚期缺失局限于部分肿瘤组织。对取自42例胃癌组织（26例进展期癌和16例早期癌）的167个肿瘤位点进行了5号染色体长臂、9号染色体短臂、13号染色体长臂、17号染色体短臂和18号染色体长臂上的LOH检测。通过对每个染色体臂使用两到三个微卫星标记，结果显示，在至少一个肿瘤位点显示LOH的29个肿瘤中，15个（51.7%，12例进展期癌和3例早期癌）在三个或更多染色体臂上存在多个缺失，其中89.4%（94个中的84个）的缺失在所有检测的肿瘤位点均一致发现。在其余14个（48.3%，8例进展期癌和6例早期癌）在一个或两个染色体臂上存在散发性缺失的肿瘤中，44%（25个中的11个）的缺失在检测的位点中共同存在。多个和散发性LOH模式在瘤内分布上的这种显著差异（P<0.001，Fisher精确检验）提示存在两种不同的LOH亚型：多个缺失（高LOH），在早期发生，伴有少量额外缺失；散发性缺失（低LOH），在肿瘤进展过程中相对较晚发生。多灶性LOH结果表明，等位基因缺失并非逐渐发生，而是以两种在早期就已确定的方式发生。
