The TP53 gene is one of the most frequently mutated genes in human cancers, with somatic mutations playing a key role in cancer development. Germline mutations in TP53 are the underlying cause of Li-Fraumeni syndrome, which increases the risk of various early-onset cancers. TP53 mutations are diverse in type, location, and structural impact, and they can serve as prognostic and predictive markers, as well as targets for pharmacological intervention. The IARC TP53 Database compiles all TP53 mutations found in human cancers, providing information on tumor phenotype, patient characteristics, and the functional impact of mutations. A human TP53 knockin mouse model (HupKi mouse) allows for the study of mutagenesis in the context of a human TP53 sequence. TP53 mutations are distributed throughout the coding sequence, with a high frequency in certain cancers such as ovarian, esophageal, and colorectal cancers. The majority of TP53 mutations are missense mutations, which cause single amino acid changes. These mutations are often found in the DNA-binding domain, with specific codons being hotspots for mutations. CpG dinucleotides are particularly prone to mutations, leading to transitions. The distribution of TP53 mutations is similar in somatic and germline mutations, with most being missense mutations. Germline mutations are associated with Li-Fraumeni syndrome and are more common than previously thought. TP53 polymorphisms, such as the P72R and Arg72Pro variants, have been studied for their potential impact on cancer susceptibility and prognosis. These polymorphisms may influence p53 function and are associated with different cancer risks. The P72R SNP has been linked to variations in cancer risk across different populations and may have a role in cancer susceptibility. However, the significance of these polymorphisms in clinical settings remains to be fully understood. TP53 mutations can have significant structural and functional impacts on p53 protein, affecting its ability to regulate cell cycle and apoptosis. Mutations can lead to loss of function, which is critical for cancer development. Some mutations may have dominant-negative effects, reducing the activity of wild-type p53. Others may have gain-of-function effects, leading to oncogenic activity. The impact of these mutations on cancer progression varies depending on the type of mutation and the cellular context. Mutagen-induced mutation spectra in human cancers can provide insights into the etiology of cancer. For example, certain mutagens are associated with specific mutation patterns in cancer. These patterns can be used to identify environmental exposures and to understand the mechanisms of carcinogenesis. Experimental systems, such as the HupKi mouse model, allow for the study of TP53 mutations in a human sequence context, providing valuable information on the effects of mutagens on TP53. In clinical settings, TP53 mutations are useful biomarkers for tumor clThe TP53 gene is one of the most frequently mutated genes in human cancers, with somatic mutations playing a key role in cancer development. Germline mutations in TP53 are the underlying cause of Li-Fraumeni syndrome, which increases the risk of various early-onset cancers. TP53 mutations are diverse in type, location, and structural impact, and they can serve as prognostic and predictive markers, as well as targets for pharmacological intervention. The IARC TP53 Database compiles all TP53 mutations found in human cancers, providing information on tumor phenotype, patient characteristics, and the functional impact of mutations. A human TP53 knockin mouse model (HupKi mouse) allows for the study of mutagenesis in the context of a human TP53 sequence. TP53 mutations are distributed throughout the coding sequence, with a high frequency in certain cancers such as ovarian, esophageal, and colorectal cancers. The majority of TP53 mutations are missense mutations, which cause single amino acid changes. These mutations are often found in the DNA-binding domain, with specific codons being hotspots for mutations. CpG dinucleotides are particularly prone to mutations, leading to transitions. The distribution of TP53 mutations is similar in somatic and germline mutations, with most being missense mutations. Germline mutations are associated with Li-Fraumeni syndrome and are more common than previously thought. TP53 polymorphisms, such as the P72R and Arg72Pro variants, have been studied for their potential impact on cancer susceptibility and prognosis. These polymorphisms may influence p53 function and are associated with different cancer risks. The P72R SNP has been linked to variations in cancer risk across different populations and may have a role in cancer susceptibility. However, the significance of these polymorphisms in clinical settings remains to be fully understood. TP53 mutations can have significant structural and functional impacts on p53 protein, affecting its ability to regulate cell cycle and apoptosis. Mutations can lead to loss of function, which is critical for cancer development. Some mutations may have dominant-negative effects, reducing the activity of wild-type p53. Others may have gain-of-function effects, leading to oncogenic activity. The impact of these mutations on cancer progression varies depending on the type of mutation and the cellular context. Mutagen-induced mutation spectra in human cancers can provide insights into the etiology of cancer. For example, certain mutagens are associated with specific mutation patterns in cancer. These patterns can be used to identify environmental exposures and to understand the mechanisms of carcinogenesis. Experimental systems, such as the HupKi mouse model, allow for the study of TP53 mutations in a human sequence context, providing valuable information on the effects of mutagens on TP53. In clinical settings, TP53 mutations are useful biomarkers for tumor cl