摘要
目的 探讨 3号染色体短臂上的抑癌基因Fhit、hMLH1及VHL在肺癌发展中的可能作用。方法 选取上述基因内含子或附近的微卫星多态位点对 45例肺癌组织进行杂合性缺失 (LOH)分析 ,并对其中 17例进行了Fhit蛋白的免疫组化染色。结果 Fhit基因内含子 3个位点D3S12 34、D3S130 0及D3S410 3的杂合率分别为 77.8% (35 / 45 )、73.3% (33/ 45 )和 82 .2 % (37/ 45 ) ,LOH阳性率分别为 6 2 .9% (2 2 / 35 )、6 3 6 % (2 1/ 33)和 5 9.5 % (2 2 / 37)。与hMLH1基因连锁的两个位点D3S15 6 1、D3S16 12杂合率分别为 48.9% (2 2 / 45 )、42 .2 % (19/ 45 ) ,LOH阳性率分别为 5 4.5 % (12 / 2 2 )和 6 3.2 %(12 / 19)。与VHL基因连锁的两个位点D3S10 38、D3S12 83的杂合率分别为 6 2 .2 % (2 8/ 45 )和 80 .0 %(36 / 45 ) ,LOH阳性率分别为 6 4 3% (18/ 2 8)和 41.7% (15 / 36 )。 17例肺癌组织有 6 4.7% (11/ 17)Fhit蛋白表达缺失。在Fhit蛋白缺失的 11个病例中 ,有 10例存在一个或多个Fhit基因位点的LOH。结论 上述 3个抑癌基因存在的高频率LOH可为肺癌的早期诊断提供新的途径和依据。Fhit基因的杂合性缺失可能是Fhit蛋白表达下调的机理之一。
Objective To investigate the allelic loss of heterozygosity in three tumor suppressor genes, Fhit, hMLH1 and VHL, located at three corresponding regions 3p14 cen,3p21.3 22 and 3p25 26 with a high fregnency in lung cancer and to evaluate the expression of Fhit protein in the tumor tissue of lung cancer. Methods Microsatellite analysis was performed by using the primers that amplified polymorphic sequences inside or flanking to the three genes in the tumor tissues collected from 45 cases of primary lung cancer. Immunohistochemical staining was performed to detect the expression of Fhit protein in the tumor tissues from 17 out of the 45 cases. Results For loci D3S1234, D3S1300 and D3S4103 that are located in the intron of Fhit gene, LOH was found in informative cases as 62.9%, 63.6% and 59.5%, respectively. In D3S1561 and D3S1612 that are linked with hMLH1 gene, LOH was detected in 54.5% and 63.2% of informative cases, respectively. LOH was found in 64.3% and 41.7% of informative cases, at D3S1038 and D3S1283, respectively, which are flanked to VHL gene. Expression of Fhit protein was down regulated in tumor tissues of 11 out of 17 cases (64.7%); among 10 of the 11 samples, LOH was detected at one or more of the microsatellite loci tested. Conclusion High frequency loss of one allele in tumor suppressor genes Fhit, hMLH1 and VHL was observed in the tumor tissues of lung cancer, indicating that it may play a role in carcinogenesis of human lung, and may provide some new approaches to early gene detection for lung cancer. Loss of one allele of Fhit gene may be one of the mechanisms for down regulation of Fhit protein expression in lung cancer.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2001年第7期399-401,共3页
National Medical Journal of China
基金
国家九五攻关基金!资助项目 (96 90 6 0 114 )
国家重点基础研究发展 973规划资助!项目 (G19980 5 12 0 7)
