RT Journal Article
SR Electronic
T1 Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000952
DO 10.26508/lsa.202000952
VO 4
IS 3
A1 Chan, Chang S
A1 Sun, Yvonne
A1 Ke, Hua
A1 Zhao, Yuhan
A1 Belete, Merzu
A1 Zhang, Cen
A1 Feng, Zhaohui
A1 Levine, Arnold J
A1 Hu, Wenwei
YR 2021
UL https://www.life-science-alliance.org/content/4/3/e202000952.abstract
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.