Institute for Advanced Study, Princeton, NJ, USA.
Oncogene. 2021 Oct;40(41):5975-5983. doi: 10.1038/s41388-021-01991-3. Epub 2021 Aug 13.
The p53 protein is a transcription factor that prevents tumors from developing. In spontaneous and inherited cancers there are many different missense mutations in the DNA binding domain of the TP53 gene that contributes to tumor formation. These mutations produce a wide distribution in the transcriptional capabilities of the mutant p53 proteins with over four logs differences in the efficiencies of forming cancers in many diverse tissue types. These inherited and spontaneous TP53 mutations produce proteins that interact with both genetic and epigenetic cellular modifiers of p53 function and their inherited polymorphisms to produce a large number of diverse phenotypes in individual patients. This manuscript reviews these variables and discusses how the combinations of TP53 genetic alterations interact with genetic polymorphisms, epigenetic alterations, and environmental factors to begin predicting and modifying patient outcomes and provide a better understanding for new therapeutic opportunities.
p53 蛋白是一种转录因子，可以防止肿瘤的形成。在自发性和遗传性癌症中，TP53 基因的 DNA 结合域存在许多不同的错义突变，这些突变有助于肿瘤的形成。这些突变导致突变 p53 蛋白的转录能力广泛分布，在许多不同组织类型中形成癌症的效率差异超过四个对数级。这些遗传性和自发性 TP53 突变产生的蛋白质与 p53 功能的遗传和表观遗传细胞修饰物相互作用，以及它们的遗传多态性，在个体患者中产生大量不同的表型。本文综述了这些变量，并讨论了 TP53 基因改变与遗传多态性、表观遗传改变和环境因素的组合如何相互作用，以开始预测和改变患者的结局，并为新的治疗机会提供更好的理解。
