黑斑—息肉综合征染色体不稳定性及肿瘤易感基因位点的分析

目的 通过对黑斑－息肉综合征（ＰＪＳ）染色体淡稳定性、基因缺失、点突变和重排的分析，确定与疾病易感的相关基因及变异方式。方法 本研究经家系调查和利用患者外周血淋巴细胞比较分析了染色体脆性位点表达；采用聚合酶反应（ＰＣＲ）、ＰＣＲ／ＳＳＣＰ分析、微卫星检测和ＤＮＡ测序分析技术对染色体脆性位点（Ｆｒａ）出现频率高的３ｐ１４的遗传标记进行检测。结果 ⑴４个家系共２２例患者，其息肉性质均为腺瘤样息肉，死于

Analysis of instability and deletion on chromosome 3p14 in Peutz-Jeghers Syndrome

OBJECTIVE: To determine the region where the tumor susceptible genes located, and to study chromosome instability, deletion and rearrangement of genes in Peutz-Jeghers Syndrome. METHODS: The method of induction was used to detect chromosome fragile sites of patients, Who were contrasted to familiar members and healthy individuals. DNA was extracted from leukocyte, polypus and tumor tissues, fresh or embedded in paraffin. The highly frequent abnormality of chromosome 3p14 region was studied with PCR, PCR-SSCP, microsatellite analysis, and DNA sequencing. RESULTS: The highest frequency of fragile site was in chromosome 3p14-3p24 region. The aberration frequency of D3S3340 is 21.4%, and that of D3S30 is 14.3%. Microsatellite analysis demonstrated LOH, of which the frequency is 42.9%; in addition, APC, k-ras mutation also occurred. The loss of guanylic acid was found in D3S1766. CONCLUSION: PJS has high chromosome instability, with deletion, mutation and arrangement of genes in 3p14 region, suggesting that cancer susceptible genes would be harbed in 3p14 cloning.