By modeling a <i>TP53</i> mutation in mice that has relatively weak cancer penetrance, this study provides <i>in vivo</i> evidence that the human R337H mutation can compromise p53 activity and promote tumorigenesis.<b>Significance:</b> A germline mutation in the oligomerization domain of p53 decreases its transactivation potential and renders mice susceptible to carcinogen-induced liver tumorigenesis.<i></i>.
However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context.
Moreover, loss of heterozygocity with retention of the R337H allele was observed in a breast adenocarcinoma, supporting a role for this mutation in breast tumorigenesis.
The mechanisms of adrenal tumorigenesis remain poorly established; the R337H germline mutation in the p53 gene has previously been associated with ACTs in Brazilian children.