膀胱移行细胞癌的进展——肿瘤组织和细胞尿液沉积物中Tp53基因突变的温度梯度和序列分析

Cancer detection and prevention Pub Date : 2000-01-01
H H Schlechte, M D Sachs, S V Lenk, S Brenner, B D Rudolph, S A Loening
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引用次数: 0

摘要

膀胱癌中p53蛋白的表达与肿瘤进展之间的关系是已知的。在本文中,我们尝试用分子遗传学技术来研究这一现象。经尿道膀胱肿瘤切除术(TURB)获得137个膀胱肿瘤组织。本文收集了72例移行细胞癌复发患者的尿液沉积物。对这些患者进行了至少三个月的随访。分别对Tp53基因的外显子5,6,7和8进行聚合酶链反应(PCR)。采用温度梯度凝胶电泳(TGGE)对PCR产物进行突变筛选。从TGGE中切除重新扩增的突变型和野生型条带的测序。137例膀胱癌标本中Tp53突变频率为43.1%,而ta肿瘤中已经有32.7%(16/49)发生Tp53突变。25例Tp53野生型肿瘤患者中有4例出现进展。在Tp53突变的癌症患者组中,12名患者中有7名出现肿瘤进展。在14例癌症组织中Tp53突变的患者中,有11例在尿液沉积物中也发现了相同的突变。在这些患者中,TURB成功治疗肿瘤导致尿沉积物中Tp53突变丢失,肿瘤复发导致复发。
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Progression in transitional cell carcinoma of the urinary bladder--analysis of Tp53 gene mutations by temperature gradients and sequence in tumor tissues and in cellular urine sediments.

The relationship between expression of p53 protein in bladder cancer and tumor progression is known. In this paper, we attempt to study this phenomenon by molecular-genetic techniques. One hundred thirty-seven bladder tumor tissues were obtained from transurethral resection (TURB). Urine sediments were collected from 72 patients suffering from transitional cell carcinoma and tumor recurrence. These patients were followed up for at least three months. Separate polymerase chain reactions (PCR) were carried out for exons 5, 6, 7, and 8 of the Tp53 gene. Temperature gradient gel electrophoresis (TGGE) was used to screen mutations in the PCR products. Sequencing from reamplified mutant and wildtype bands was excised from the TGGE. Tp53 mutation frequency is 43.1% in 137 bladder cancer specimens, but already 32.7% of Ta-tumors (16/49) were Tp53 mutated. Four of 25 patients with Tp53 wild-type tumors suffered from progression. In the group of patients with Tp53 mutated cancer, seven of 12 had a tumor progression. In 11 of 14 patients with Tp53 mutation in cancer tissue, the same mutation was also found in urine sediments. In such patients, successful tumor treatment by TURB results in loss of their Tp53 mutation in urine sediment, and tumor recurrency resulted in reappearance.

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