喉癌三号染色体短臂(3p)抑癌基因微卫星多态位点的杂合性缺失检测  

Loss of heterozygosity of tumor suppressor genes on chromosome 3p in laryngeal squamous cell carcinoma by microsatellite analysis

作　　者：徐先发[1] 李立[2] 张建军[2] 高燕宁[2] 张瑞华[1] 唐平章[2] 程书钧[2] 

机构地区：[1]首都医科大学附属北京朝阳医院耳鼻咽喉-头颈外科,100020 [2]中国医学科学院中国协和医科大学肿瘤医院肿瘤研究所

出　　处：《耳鼻咽喉（头颈外科）》2002年第4期231-235,共5页Chinese Arch Otolaryngology-Head Neck Surg

摘　　要：目的 :检测喉鳞癌组织在 3号染色体短臂上 (3p)三个区段 3p14 - cen、3p2 1- 2 2、3p2 5 - 2 6内相应抑癌基因FHIT,h ML H1及 VHL微卫星 (microsatellite,MS)的杂合性缺失 (loss of heterozygosity,L OH)。方法 :采用显微切割法从病理切片中挑取肿瘤组织 ,选取上述基因内含子或与其连锁的 7个 MS多态位点对 4 1例喉癌组织进行聚合酶链式反应和变性凝胶电泳。结果 :FHIT基因内含子三个 MS位点 D3S12 34、D3S130 0及 D3S4 10 3的 L OH发生率分别为77.4 2 %、6 8.97%和 6 9.70 %。与 h ML H1基因连锁的两个 MS位点 D3S15 6 1和 D3S16 12的 L OH发生率分别为 5 8.33%和 4 5 .16 %。与 VHL基因连锁的两个 MS位点 D3S10 38及 D3S12 83的 L OH发生率分别为 4 3.33%和 4 6 .88%。 FHIT基因内含子的 MS,与 h ML H1基因连锁的 MS,与 VHL基因连锁的 MS的 L OH发生率分别为 82 .93% (34/ 4 1) ,6 7.5 0 % (2 7/ 4 0 ) ,70 .0 % (2 8/ 4 0 )。同时在上述三个基因区域内发生某一或某些 MS多态位点 L OH者有 16例 ,占 39%。D3S12 34L OH在吸烟指数≥ 4 0 0的喉癌患者较吸烟指数 <4 0 0者明显频发 ,统计学有显著性差异 (P <0 .0 5 )。结论 :喉癌组织 3号染色体短臂上三个抑癌基因 FHIT,h ML H1及 VHL存在高频率的 LObjective: To investigate loss of heterozygosity (LOH) of three tumor suppressor genes, FHIT, hMLH1 and VHL, located at three corresponding regions 3p14\|cen,3p21 3\|22 and 3p25\|26 in laryngeal squamous cell carcinoma. Methods: With the microdissected tumor tissues derived from 41 cases of laryngeal squamous cell carcinoma, mircrosatellite analysis was applied using the primers that amplified polymorphic sequences inside of or flanking to the three genes. Results: For loci D3S1234, D3S1300 and D3S4103 that are located in the intron of FHIT gene, LOH was found in informative cases as 77.42%, 68.97% and 69.70%, respectively. In D3S1561 and D3S1612 that are linked with hMLH1 gene, LOH was detected as 58.33% and 45.16% of informative cases, respectively. LOH was found in 43.33% and 46.88% of informative cases at D3S1083 and D3S1283, respectively, which are flanked to VHL gene. MS LOH in FHIT, hMLH1 and VHL gene was found in informative cases as 82.93%(34/41), 67.50%(27/40) and 70.0%(28/40), respectively. At the above\|mentioned three genes, there were one or some MS LOH in 16 patients (39%) at the same time. There was statistically significant difference in the rate of LOH only at D3S1234 between the patients smoking index≥ 400 and those with the index<400 (P<0 05). Conclusion: High frequency of loss of one allele in tumor suppressor genes FHIT, hMLH1 and VHL was observed in the laryngeal squamous cell carcinoma, indicating that it may play a role in carcinogenesis of laryngeal cancer and may provide some new approaches for early gene detection for laryngeal cancer.

关 键 词：喉癌 三号染色体短臂 抑癌基因 微卫星多态位点 杂合性缺失 诊断 

分 类 号：R739.65[医药卫生—肿瘤]