The Li-Fraumeni syndrome (LFS) is characterised clinically by the appearance of tumours in multiple organs, generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumour suppressor gene p53.

We present here the case of a patient aged 40 with the diagnosis of LFS who presented with premenopausal breast cancer. She had a positive family history of cancer. As a consequence, she was referred to genetic counselling. Genetic analysis revealed a TP53 germline mutation, which is diagnostic for LFS. However, further genetic analysis of different tissues showed a genetic mosaicism in our patient.

Patients with LFS have a high risk for a broad spectrum of tumours. The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives. Targeted next-generation sequencing represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype. Theoretically, since mosaics do not have mutations in all of their cells, the cells that do not have mutant p53 are less likely to undergo malignant transformation or have the same risk of everyone else.

(BELG J MED ONCOL 2020;14(3):100–105)