Kdy má smysl hledat v rodinách onkologickýchpacientů zárodečné mutace v genu TP53?

Significance of TP53 Gene Identification in Tumour Affected Families

Background.
The Li-Fraumeni syndrome is a relatively rare familial cancer syndrome associated with germlinemutations in the tumour-suppressor gene TP53. Members of affected families can suffer from a wide variety oftumours. Identification of a germline TP53 mutation is particularly important in families of patients affected by oneof several characteristic types of tumours.Methods and Results. The data used for the distribution analysis of mean age at the cancer diagnosis in TP53mutation carriers and in the Czech population were extracted from a database of 176 families (469 cancers in 346patients) with germline TP53 mutations and from Czech statistical data of cancer incidence in years 1994 to 1998(ÚZIS). The comparison of the age distribution of the relative tumour incidence in these two groups clearly separatedchildhood adrenocortical sarcoma, rhabdomyosarcoma, osteosarcoma and brain tumour patients. In their familiesgenetic counselling should be recommended.Conclusions. Patients with low age at diagnosis of these tumours, particularly patients with additional personal orfamily history of malignancy, should be considered as potential TP53 mutation carriers. It should be relevant notonly for the treatment and follow-up of the patients but also for preventive measures aimed at other members of theirfamilies.

Key words:
familial predisposition, cancer, germline mutations, TP53 gene, sarcoma, adrenocortical carcinoma,breast cancer, brain tumour.