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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。
OBJECTIVE: To analyze the loss of heterozygosity (LOH) in the whole genome of nasopharyngeal carcinoma (NPC) and to locate the region of high frequency LOH in NPC, so as to provide a molecular genetic basis for mapping NPC related genes. Methods: 98 cases of NPC tumor genomic DNA alleles were detected by PCR microsatellite polymorphism (335 loci). RESULTS: Among the 22 pairs of chromosomes, 19 pairs of chromosomes had at least one loci with ≥30% LOH frequency in the selected loci. There were no more than 30% LOH frequency on chromosome 3 (No.15, No.2 and No.22) Point. Of the 335 loci, LOH frequency was ≥60% at 4 loci, of which 3 were on chromosome 3 and 1 was on chromosome 9, and the frequency of LOH was about 50% -59% at 5 loci, among which 3 One locus on chromosome 3, one on chromosome 5 and one on chromosome 11; the frequency of LOH was between 40% and 49% at 22 loci and the frequency of LOH was between 30% and 39% at 52 loci; 252 loci LOH frequency less than 30%, suggesting that the background is missing; LOH frequency ≥ 30% of the sites mainly concentrated in 12 chromosome arms, located in: 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. The new report of this study in the chromosomal band 1p, 5q and 19q and other high-frequency LOH, LOH fine map suggest that these areas may exist in NPC-related TSG. CONCLUSION: It is a common molecular event that NPC tumor cells produce high frequency LOH in multiple chromosomal regions, suggesting that there may exist tumor suppressor genes that play an important role in the occurrence and development of NPC in these missing regions.