p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer
p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer
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DOI：
10.1159/000019778
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发表时间：
1998-11-01
期刊：
影响因子：
23.4
通讯作者：
Loening, SA
中科院分区：
文献类型：
--
作者：
Schlechte, H;Lenk, SV;Loening, SA
目的：目的：应用温度梯度凝胶电泳（TGGE）和测序技术，检测和分析良性前列腺增生（BPH）组织中p53抑癌基因（Tp 53）的点突变。材料和方法：141例组织标本（约100例）。经尿道前列腺电切术（TURP）后，12例标本经穿刺活检后。用于遗传分析的对照样品是（a）7个没有任何BPH和恶性肿瘤迹象的前列腺组织和（B）103个前列腺癌（PCa）组织。扩增关键的Tp 53外显子5-8的DNA，并在限定的温度条件（TGGE）下在水平聚丙烯酰胺凝胶上电泳，以产生特定的凝胶位移和突变情况下的同源和异源双链体组。用激光荧光电泳装置从再扩增的突变体和野生型条带进行测序。结果如下：对153例BPH标本进行TGGE筛查，发现29例标本存在Tp 53突变（5例在外显子5，11例在外显子6，12例在外显子7，3例在外显子8; 1例组织标本同时显示3个外显子突变）。计算的突变频率为19.0%。2例BPH组织突变患者在TURF后2-3年发生PCa。1例BPH组织突变患者发生膀胱癌。在118名BPH患者中，没有一名已知患有泌尿系统癌症。103例PCa标本中Tp 53突变率为26.2%。BPH和PCa的突变频率仅在第5外显子突变计数较低时有显著性差异。结论：BPH组织中Tp 53基因突变可能是其肿瘤发生的危险因素。
Objectives: To identify and analyse point mutations in p53 tumour suppressor gene (Tp53) in benign prostatic hyperplasia (BPH) by temperature gradient gel electrophoresis (TGGE) and sequence. Materials and Methods: 141 tissue specimens (approx. 100 mg) after transurethral resection of the prostate (TURP), 12 specimens after needle biopsy. Control samples for genetic analysis were (a) 7 prostate tissues without any sign of BPH and malignancy and (b) 103 prostate cancer (PCa) tissues. DNA of the critical Tp53 exons 5-8 was amplified and run on horizontal polyacrylamide gels under defined temperature conditions (TGGE) to yield specific gel shifts and sets of homo- and heteroduplexes in case of mutation. Sequencing with a laser-fluorescent electrophoresis unit was done from re-amplified mutant and wild-type bands. Results: TGGE screening of 153 BPH samples identified 29 specimens with Tp53 mutations (5 in exon 5, 11 in exon 6, 12 in exon 7, 3 in exon 8; 1 tissue sample showed mutations in 3 exons at a time). The computed mutation frequency was 19.0%. Two patients, with mutation in BPH tissue, developed PCa 2-3 years after TURF. One patient with mutation in BPH tissue developed bladder cancer. Of 118 patients with non-mutated DNA in BPH, none is known to have a urological cancer. The Tp53 mutation frequency in 103 PCa samples was 26.2%. Significant differences of mutation frequency between BPH and PCa were detected only in lower exon 5 mutation counts in BPH. Conclusion: Tp53 mutation in BPH tissue may be a tumour risk factor.