Borkowska Edyta, Binka-Kowalska Aleksandra, Constantinou Maria, Nawrocka Agnieszka, Matych Józef, Kałuzewski Bogdan
Department of Medical Genetics, Medical University of Łódz, and Department of Urology and Kidney Transplantation, Pirogow Hospital, Poland.
J Appl Genet. 2007;48(2):177-83. doi: 10.1007/BF03194676.
The present study aimed at detection of P53 gene mutations in cells of urinary bladder neoplasms, as the mutations may be regarded as an independent prognostic factor for progression and recurrence of tumours. In the study, 82 patients with clinically diagnosed urinary bladder tumour were included. The control was composed of DNA samples from urine and blood of 202 healthy patients. Exons 5-8 of the P53 gene were screened for mutations by using multitemperature single-strand conformational polymorphism (MSSCP) analysis. Samples with abnormal MSSCP patterns were subjected to direct sequencing. The frequency of mutations in exons 5-8 of the P53 gene in patients with bladder cancer was lower (3.3% in grade G1, 24% in G2, and 39% in G3) than the data reported in the literature. We found a higher percentage of polymorphism at codon 213 of the P53 gene in bladder cancer patients (6%), compared with the values in the reference group (2.5%). These results were matched with those of the loss of heterozygosity (LOH) analysis. In conclusion, mutations were found mainly in more advanced histopathological and clinical stages of the disease and at the CIS stage (carcinoma in situ). It cannot be excluded that the observed polymorphism at codon 213 may be a predisposing factor for urinary bladder carcinoma development.
本研究旨在检测膀胱肿瘤细胞中的P53基因突变，因为这些突变可能被视为肿瘤进展和复发的独立预后因素。在该研究中，纳入了82例临床诊断为膀胱肿瘤的患者。对照组由202例健康患者的尿液和血液DNA样本组成。通过多温度单链构象多态性（MSSCP）分析筛选P53基因的外显子5-8中的突变。MSSCP模式异常的样本进行直接测序。膀胱癌患者中P53基因外显子5-8的突变频率低于文献报道的数据（G1级为3.3%，G2级为24%，G3级为39%）。我们发现，与参考组（2.5%）相比，膀胱癌患者中P53基因第213密码子的多态性百分比更高（6%）。这些结果与杂合性缺失（LOH）分析的结果相符。总之，突变主要发生在疾病的更晚期组织病理学和临床阶段以及原位癌（CIS）阶段。不能排除观察到的第213密码子多态性可能是膀胱癌发生的一个易感因素。
