The strong clinical association between pediatric ACC and Li-Fraumeni Syndrome (LFS) [31], coupled with the paradoxical overexpression of p53 in the tumor, led us to hypothesize that the p53 T253I mutation may be pathogenic and represent a loss-of-function mutation, similar to R213X and C176Y, two other known LFS-associated variants [14,15]. This evidence concerns the gene TP53 and Li-Fraumeni syndrome.