Li–Fraumeni Syndrome

Abstract Li–Fraumeni syndrome is a rare inherited predisposition to the development of multiple cancer phenotypes at an early age which is attributed primarily to germline mutations of the TP53 tumour suppressor gene. p53 plays a major role in the control of cellular growth, cell cycle arrest, DNA repair, apoptosis and senescence, particularly in response to DNA damage and other cellular stressors. The tumours most closely associated with LFS are called ‘core’ cancers and include soft tissue sarcomas, osteosarcoma, premenopausal breast cancer, brain tumours and adrenocortical carcinomas. Identification of these families is important in the study of cancer and the development of ethical and appropriate screening modalities, prevention, early cancer detection and treatment of individuals who harbour alterations of such cancer genes, in order that we may one day improve their prognosis. Key Concepts Li‐Fraumeni syndrome is caused by germline TP53 mutations. p53 is fundamental to DNA damage repair and genome stability. Li‐Fraumeni syndrome is associated with a wide range of early‐onset cancers. Comprehensive surveillance of TP53 mutation carriers is associated with early tumor detection and improved clinical outcomes. There are currently no effective pharmacologic measures to prevent cancer in TP53 mutation carriers.