PT  - JOURNAL ARTICLE
AU  - Chang S Chan
AU  - Yvonne Sun
AU  - Hua Ke
AU  - Yuhan Zhao
AU  - Merzu Belete
AU  - Cen Zhang
AU  - Zhaohui Feng
AU  - Arnold J Levine
AU  - Wenwei Hu
TI  - Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models
AID  - 10.26508/lsa.202000952
DP  - 2021 Mar 01
TA  - Life Science Alliance
PG  - e202000952
VI  - 4
IP  - 3
4099  - https://www.life-science-alliance.org/content/4/3/e202000952.short
4100  - https://www.life-science-alliance.org/content/4/3/e202000952.full
SO  - Life Sci. Alliance2021 Mar 01; 4
AB  - 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.