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Li-Fraumeni syndrome is an inherited fault in the TP53 gene giving a lifetime cancer risk near 100% in women and ~75% in men, with sarcomas, breast cancer, brain tumours, adrenal cancer and leukaemias often in childhood. Whole-body MRI surveillance saves lives.
Described by Li and Fraumeni (1969); germline TP53 mutations identified 1990 (Malkin). Core cancers: soft-tissue and bone sarcoma, premenopausal breast cancer, brain tumours (choroid plexus carcinoma, medulloblastoma SHH, glioma), adrenocortical carcinoma (~50-80% of childhood ACC carry germline TP53; R337H founder mutation in southern Brazil with 0.3% carrier frequency), leukaemia (hypodiploid ALL), and radiation-induced second cancers (radiotherapy avoided where possible). The 'Toronto protocol' (Villani, Lancet Oncol 2011, 2016) of annual whole-body MRI, brain MRI, breast MRI, ultrasound and biochemical screening detected tumours early and improved survival; now standard (NCCN, AACR 2017 consensus). Risk-reducing mastectomy is offered. Chompret criteria guide testing; ~1 in 5,000-20,000 prevalence; mosaic and low-penetrance variants complicate counselling; clonal haematopoiesis can mimic germline TP53 on blood testing.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
This review fixed the picture of p53 as the guardian of the genome that every textbook uses. It explains why TP53-mutant cancers are aggressive and hard to treat, why MDM2 inhibitors are being developed to reactivate wild-type p53, and why germline TP53 testing matters in families.
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tag hereditary.
Shares Hereditary cancer syndromes, Germline vs somatic mutations, TP53 and the tag hereditary.
Shares Hereditary cancer syndromes, Germline vs somatic mutations and the tag hereditary.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, TP53-mutated (p53-abnormal), TP53.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, TP53-mutated (p53-abnormal), The p53 network (guardian of the genome), TP53.
Shares Levine 1997: p53, the cellular gatekeeper for growth and division, TP53-mutated (p53-abnormal), The p53 network (guardian of the genome), TP53.
Shares Whole-body MRI, TP53, Sarcomas (soft tissue, bone, GIST).
Shares The Hospital for Sick Children (SickKids), Medulloblastoma, Osteosarcoma.