Choi S W, Park S W, Lee K Y, Kim K M, Chung Y J, Rhyu M G
Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul.
Oncogene. 1998 Nov 19;17(20):2655-9. doi: 10.1038/sj.onc.1202188.
To gain an insight into the genetic events underlying morphological phenotypes, we analysed 58 gastric carcinoma tissues for the genome-wide allelotype study using microsatellite markers. Based on a binomial distribution, loss of heterozygosity (LOH) that was significantly more frequent than expected (P<0.05) thus interpreted as nonrandom LOH selected during tumorigenesis. The overall extent of chromosomes undergoing LOH i.e. fractional allelic loss (FAL, the ratio of LOH-positive markers to the total number of informative markers) was measured in each tumor patient. Nonrandom LOH was found on 17p (48.0%), 18q (38.4%), 13q (38.1%) and 9p (36.4%). Overall, there were no significant phenotypes correlated with allelic loss on specific chromosome regions. Based on a bimodal distribution of FAL values with two peaks bordered by a mean of 0.233, tumors were classified into LOH-related (>0.233) and LOH-unrelated (<0.233) types. Among 24 patients with LOH-related tumors, increase in the infiltrative type of growth pattern was found to correspond with a significant trend of increasing FAL values. This study shows that the growth pattern of gastric carcinoma is correlated with FAL, suggesting that a malignant phenotype is influenced by LOH event.
为深入了解形态学表型背后的遗传事件，我们使用微卫星标记对58例胃癌组织进行了全基因组等位基因分型研究。基于二项分布，杂合性缺失（LOH）若显著高于预期频率（P<0.05），则被解释为肿瘤发生过程中选择的非随机LOH。在每位肿瘤患者中测量发生LOH的染色体的总体范围，即部分等位基因缺失（FAL，LOH阳性标记与信息性标记总数的比率）。在17p（48.0%）、18q（38.4%）、13q（38.1%）和9p（36.4%）上发现了非随机LOH。总体而言，特定染色体区域的等位基因缺失与显著的表型无关。基于FAL值的双峰分布，两个峰值以平均值0.233为界，肿瘤被分为与LOH相关（>0.233）和与LOH无关（<0.233）类型。在24例与LOH相关肿瘤的患者中，浸润性生长模式的增加与FAL值增加的显著趋势相对应。本研究表明，胃癌的生长模式与FAL相关，提示恶性表型受LOH事件影响。
