具有家族史鼻咽癌4p15.1-4q12区等位基因杂合性丢失分析

目的确定有家族史鼻咽癌患者4p15．1-4q12区域等位基因杂合性丢失（loss of heterozygosity，LOH）的分布和频率，为进一步缩小该区域内易感基因的范围提供新的线索和依据。方法收集具有家族史的鼻咽癌患者石蜡包埋的活检组织标本，采用显微切割的方法在肿瘤组织石蜡切片上分离肿瘤细胞和正常淋巴细胞，选定7个定位于4p15．1-4q12区域内的高密度微卫星位点，多重PCR扩增和丙烯酰胺凝胶电泳后，Genescan软件对各位点LOH进行分析。结果25例具家族史鼻咽癌患者中，23例在4p15．1-4q12区至少存在一个微卫星位点的LOH（92％）。其中D4S2382位点LOH的频率最高，达到56％；D4S350和D4S1547位点LOH频率均约为50％。最小共同缺失区位于位点D4S350和D4S1547之间。结论鼻咽癌4p15．1—4q12区域内的易感基因可能位于微卫星位点D4S350和D4S1547附近。

Loss of heterozygosity in the region of chromosome 4p15.1-4q12 in nasopharyngeal carcinoma patients with familial history

Objective To analyze the allelic loss of heterozygosity (LOH) in the region of chromosome 4p15.1-4q12 in nasopharyngeal carcinoma (NPC) patients with family history. Methods Tumor cells and lymphocytes were obtained from paraffin-embedded biopsied tissue section by microdissection. LOH detections were carried out on 25 NPC patients with family history by PCR-based microsatellite polymorphism analysis using 7 pairs of microsatellite markers primers. The microsatellite loci located in 4p15.1-4q12 region. Genescan software was used to analyse LOH at each locus. Results Ninety-two percent of NPC cases (23/25) with family history was showed at least one microsatellite marker of LOH. Higher frequencies of LOH were found at three loci: D4S238 (56%), D4S350 (50%), D4S1547 (50%). The minimal common region of deletion might be defined between D4S350 and D4S1547. Conclusion The higher incidence of LOH at D4S350 and D4S1547 suggests that there may be a potential tumor suppressor gene located in the two regions.