Group of Molecular Carcinogenesis, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001008. doi: 10.1101/cshperspect.a001008.
Somatic mutations in the TP53 gene are one of the most frequent alterations in human cancers, and germline mutations are the underlying cause of Li-Fraumeni syndrome, which predisposes to a wide spectrum of early-onset cancers. Most mutations are single-base substitutions distributed throughout the coding sequence. Their diverse types and positions may inform on the nature of mutagenic mechanisms involved in cancer etiology. TP53 mutations are also potential prognostic and predictive markers, as well as targets for pharmacological intervention. All mutations found in human cancers are compiled in the IARC TP53 Database (http://www-p53.iarc.fr/). A human TP53 knockin mouse model (Hupki mouse) provides an experimental model to study mutagenesis in the context of a human TP53 sequence. Here, we summarize current knowledge on TP53 gene variations observed in human cancers and populations, and current clinical applications derived from this knowledge.
TP53 基因中的体细胞突变是人类癌症中最常见的改变之一，而种系突变是 Li-Fraumeni 综合征的根本原因，Li-Fraumeni 综合征使患者易患多种早发性癌症。大多数突变是分布在整个编码序列中的单碱基替换。它们的不同类型和位置可以提示参与癌症病因的诱变机制的性质。TP53 突变也是潜在的预后和预测标志物，也是药物干预的靶点。在人类癌症中发现的所有突变都被汇编在 IARC TP53 数据库中（http://www-p53.iarc.fr/）。人类 TP53 基因敲入小鼠模型（Hupki 小鼠）为研究人类 TP53 序列背景下的突变提供了一个实验模型。在这里，我们总结了目前在人类癌症和人群中观察到的 TP53 基因变异的知识，以及从这些知识中得出的当前临床应用。
