[Germline mutations of the p53 gene].

Germline mutations of the p53 gene are associated to the Li-Fraumeni, a rare autosomal dominant syndrome characterized by a wide spectrum of tumours including sarcomas, breast carcinomas, brain tumors and adrenocortical carcinomas. In most of the cases, tumours will develop in children and young adults. Germline p53 mutations have been identified in approximately 50% of the families with the Li-Fraumeni syndrome, and in families which only partially fulfilled the definition of the syndrome. Germline p53 mutations are mostly missense mutations, located between exon 5 and exon 8, within the DNA-binding domain of p53 and these mutations inactivate the transcriptional activity of the protein. In tumours, the wild-type allele is usually lost, which indicates, that p53 inactivation fits the Knudson model. Identification of a germline p53 mutation in an affected subject allows to establish the diagnosis of the Li-Fraumeni syndrome on a molecular basis and screening for germline p53 mutations may be performed in 1) families including two first degree relatives with cancers belonging to the Li-Fraumeni spectrum, one relative being affected before age 45, 2) children or young adults with a rare tumour of in the general population, belonging to the Li-Fraumeni spectrum, such as adrenocortical carcinoma, and 3) children or young adults under age 45 with multiple primary tumours of the Li-Fraumeni spectrum. In contrast, the clinical benefit of identifying germline p53 mutations carriers in affected families, considering the wide spectrum of tumours associated to this syndrome, remains to be established.