Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models.
Life Sci Alliance
; 4(3)2021 03.
Article
em En
| MEDLINE
| ID: mdl-33376133
ABSTRACT
p53 is the most frequently mutated gene in human cancers. Li-Fraumeni syndrome patients inheriting heterozygous p53 mutations often have a much-increased risk to develop cancer(s) at early ages. Recent studies suggest that some individuals inherited p53 mutations do not have the early onset or high frequency of cancers. These observations suggest that other genetic, environmental, immunological, epigenetic, or stochastic factors modify the penetrance of the cancerous mutant Tp53 phenotype. To test this possibility, this study explored dominant genetic modifiers of Tp53 mutations in heterozygous mice with different genetic backgrounds. Both genetic and stochastic effects upon tumor formation were observed in these mice. The genetic background of mice carrying Tp53 mutations has a strong influence upon the tissue type of the tumor produced and the number of tumors formed in a single mouse. The onset age of a tumor is correlated with the tissue type of that tumor, although identical tumor tissue types can occur at very different ages. These observations help to explain the great diversity of cancers in different Li-Fraumeni patients over lifetimes.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Proteína Supressora de Tumor p53
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Síndrome de Li-Fraumeni
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Mutação em Linhagem Germinativa
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Carcinogênese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci Alliance
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos