IDENTIFICATION OF P53 GENE-MUTATIONS IN BLADDER CANCERS AND URINE SAMPLES
IDENTIFICATION OF P53 GENE-MUTATIONS IN BLADDER CANCERS AND URINE SAMPLES
复制标题
DOI：
10.1126/science.2024123
复制
发表时间：
1991-05-03
期刊：
影响因子：
56.9
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
--
作者：
SIDRANSKY, D;VONESCHENBACH, A;VOGELSTEIN, B
虽然膀胱癌非常常见，但对其分子发病机制知之甚少。 在这项研究中，浸润性膀胱癌的p53抑制基因的基因突变的存在进行了评估。 在评估的18个肿瘤中，发现11个（61%）有p53基因的改变。 这些改变包括导致单个氨基酸取代的10个点突变和一个24碱基对缺失。 在所有的情况下，除了一个，突变与染色体17 p等位基因缺失，留下的细胞只有突变形式的p53基因产物。 通过使用聚合酶链反应和寡聚体特异性杂交，在三名受试患者的尿沉渣中发现1%至7%的细胞存在p53突变。 p53突变是第一个被证明在高比例的原发性浸润性膀胱癌中发生的遗传改变。 离体检测这种突变对于监测肿瘤细胞在体外脱落的个体具有临床意义。
Although bladder cancers are very common, little is known about their molecular pathogenesis. In this study, invasive bladder cancers were evaluated for the presence of gene mutations in the p53 suppressor gene. Of 18 tumors evaluated, 11 (61 percent) were found to have genetic alterations of p53. The alterations included ten point mutations resulting in single amino acid substitutions, and one 24-base pair deletion. In all but one case, the mutations were associated with chromosome 17p allelic deletions, leaving the cells with only mutant forms of the p53 gene product. Through the use of the polymerase chain reaction and oligomer-specific hybridization, p53 mutations were identified in 1 to 7 percent of the cells within the urine sediment of each of three patients tested. The p53 mutations are the first genetic alterations demonstrated to occur in a high proportion of primary invasive bladder cancers. Detection of such mutations ex vivo has clinical implications for monitoring individuals whose tumor cells are shed extracorporeally.