Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome.

Most p53 mutations identified in Li-Fraumeni syndrome (LFS) are missense mutations; splicing mutations have rarely been reported. A novel splicing p53 mutation was identified in a patient with Li-Fraumeni-like syndrome (LFL). Usually, p53 missense mutants identified in LFS and cancer cells function as dominant negative mutations interfering with wild-type p53 function. However, the mechanism by which p53 haploinsufficiency causes carcinogenesis is not well characterized. In this study, we describe a novel splicing mutation that results in the loss-of-function of p53. These findings suggest a linkage between the loss-of-function type p53 mutation and a LFL phenotype.