Germline alterations of TP53 that lead exclusively to loss of function are therefore associated with a later age of tumour onset and the presence of such mutations should be considered in atypical LFS families with tumours diagnosed after 40 years.
The frequent identification of de novo germline mutations emphasizes the importance of mutational analyses of the TP53 gene particularly in young patients with malignancies typical for LFS, but without a positive family history of this tumor syndrome.
In addition to these features of sporadic cancers, some individuals inherit mutant forms of p53 and consequently suffer from Li-Fraumeni syndrome, showing genetic predisposition to certain malignancies.