p53 mutations and MDM-2 amplification in renal cell cancers.
p53 mutations and MDM-2 amplification in renal cell cancers.
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发表时间：
1994-09
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通讯作者：
Y. Imai;T. Strohmeyer;M. Fleischhacker;D. Slamon;H. Koeffler
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作者：
Y. Imai;T. Strohmeyer;M. Fleischhacker;D. Slamon;H. Koeffler
采用聚合酶链反应和单链构象多态性分析，筛选了53例原发性人肾细胞肿瘤肿瘤抑制基因p53突变的基因组DNA，并对其进行了直接测序。5例出现活动能力变化。测序结果显示2例无义突变（密码子182、192），1例错义突变（密码子285），2例密码子213无义突变。与报道的肾细胞癌中17p （p53的位置）等位基因丢失的频率（15% ~ 65%）相比，改变p53的突变频率（3/53 = 6%）较低，这表明p53基因区域可能存在另一种肿瘤抑制基因，该基因发生突变时与这些癌症有关。3例p53突变的肿瘤均为预后较差的病例，即最高病理分级和/或Robson晚期。在肾细胞肿瘤中，人体内相当于小鼠双分钟-2的基因没有扩增。总之，p53的改变可能与更高级别和/或分期的肾细胞癌的发展有关。
Genomic DNA from 53 primary human renal cell tumors was screened for the presence of mutations in the tumor suppressor gene p53, using the polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct sequencing of DNA. Five cases showed mobility shifts. Sequencing of these samples revealed two cases of nonsense mutations (codons 182, 192), one case of a missense mutation (codon 285), and two cases of silent mutations at codon 213. The frequency of mutations altering the p53 (3/53 = 6%) was low when compared with the reported frequencies (15% to 65%) of allelic loss of 17p (location of p53) in renal cell cancers, suggesting the possible existence of another tumor suppressor gene in the region of the p53 gene, which when mutated is associated with these cancers. All three tumors with p53 mutations were cases with poor prognosis, i.e., highest pathological grade and/or advanced Robson stage. The human equivalent of the murine double-minute-2 was not amplified in the renal cell tumors. In summary, alterations of p53 may be associated with the development of renal cell carcinoma of higher grade and/or stage.