Missense mutations in the TP53-binding domain predominate, and >30% of these occur in just eight codons. Dominant negative properties of mutant p53, taken together with the mutation susceptibility of the nucleotides in the codon, are believed to explain the prevalence of specific mutations, including hot spots. We analyzed multiple tumor types and found no difference in clinical characteristics or survival between patients with dominant negative p53 mutant tumors and those with TP53 mutations that are predicted to be non-dominant negative. The rate tumors underwent loss of heterozygosity in these respective mutation classes was nearly identical, suggesting that presence of stable, mutant protein with predicted dominant negative activity does not reduce selective pressure to inactivate the wild-type allele. Our data suggest all inactivating mutations of TP53 are equal, and the frequency of dominant negative, hot spot mutations is likely driven more by the relative mutability of the DNA at specific codons.

TP53结合域中的错义突变占主导地位，其中超过30％的突变仅发生在8个密码子中。突变体p53的显着负性特征与密码子中核苷酸的突变敏感性一起被认为可以解释包括热点在内的特定突变的普遍性。我们分析了多种肿瘤类型，发现显性阴性p53突变型肿瘤患者与TP53阴性患者的临床特征或生存率无差异预测为非显性阴性的突变。这些相应突变类别中的肿瘤经历杂合性丧失的速率几乎相同，这表明具有预测的显性负活性的稳定突变蛋白的存在并不会降低灭活野生型等位基因的选择性压力。我们的数据表明TP53的所有失活突变都是相同的，显性负热点突变的频率可能更多地由DNA在特定密码子上的相对可变性驱动。