【摘要】 目的:分析鼻咽癌(nasopharyngealcarcinoma,NPC)全基因组染色体杂合性缺失(lossofheterozygosity,LOH),定位NPC发生高频率LOH的区域,为定位NPC相关基因提供分子遗传学依据。方法:用PCR微卫星多态性分析(335个位点)技术检测98例NPC肿瘤基因组DNA等位基因缺失。结果:在22对染色体中,19对染色体在所选取位点中有至少1个位点LOH频率≥30%,3对染色体(15号、20号和22号)无LOH频率大于30%的位点;在335个位点中,4个位点LOH频率≥60%,其中3个在3号染色体,1个在9号染色体;5个位点LOH频率介于50%～59%,其中3个在3号染色体,5号和11号染色体各1个位点;22个位点LOH频率介于40%～49%,52个位点LOH频率介于30%～39%;252个位点LOH频率低于30%,提示为背景缺失;LOH频率≥30%的位点主要集中于12个染色体臂,分布于:1p36-34,3p24-26,3p14-21,3q25-27,4q35-31,5q15-21和5q32-33,8p22-23,9p21-23和9q33-34,11p12-14,11q13-23,13q13-14和13q31-32,14q11-13,14q23-24,14q32。本研究新报道在染色体区带1p,5q和19q等发生高频率LOH,LOH精细图谱提示这些区域内可能存在与NPC相关的TSG。结论:NPC肿瘤细胞在多染色体区带发生高频率LOH是常见的分子事件,提示在这些缺失区,可能存在与NPC发生、发展过程中起重要作用的肿瘤抑制基因。更多还原

【Abstract】 Objectives: To analyze the genome wide loss of heterozygosity (LOH) and to localize the high frequent LOH regions in nasopharyngeal carcinoma (NPC), in order to provide molecular genetic evidence for localizing NPC related tumor genes. Methods: The PCR based microsatellite polymorphism analysis technique was performed on 98 cases of sporadic primary NPC by using a large panel of 335 polymorphism markers. Results: In the 22 chromosomes, at least one locus showed LOH frequency more than 30% on 19 chromosomes, and there was no locus showed LOH frequency more than 30% on three chromosomes (chromosomes 15, 20 and 22). Of the 335 informative markers, 4 loci showed LOH frequency ≥60%, 3 of them are located on chromosome 3 and 1 is located on chromosome 9; 5 loci showed LOH frequency from 50% to 59%, three of them are located on chromosome 3, and 1 on chromosome 5 and 11; 22 loci showed LOH frequency from 40% to 49%, and 52 loci showed LOH frequency from 30% to 39%; the other 252 loci showed LOH frequency less than 30% indicated that of background losses in NPC. The high frequent LOH loci (more than 30%) were clustered to 12 chromosomal arms which distributed to 1p36 34, 3p24 26, 3p14 21, 3q25 27, 4q35 31, 5q15 21 and 5q32 33, 8p22 23, 9p21 23 and 9q33 34, 11p12 14, 11q13 23, 13q13 14 and 13q31 32, 14q11 13, 14q23 24, 14q32. Moreover, the authors also firstly reported high frequent LOH on chromosome 1p, 5q and 19q, and the LOH deletion map indicated that there may be NPC related tumor suppressor genes located at these deleted regions. Conclusions: Our results indicate that high frequent LOH occurred on multiple chromosomal arms in NPC were common genetic events, and there may exist TSGs which play an important role in the development and progression of NPC in the deleted chromosomal regions.更多还原