{"entity":{"id":"li-fraumeni","kind":"term","name":"Li-Fraumeni syndrome (germline TP53)","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Li–Fraumeni_syndrome","links":[{"label":"Toronto protocol (Lancet Oncol 2016)","url":"https://doi.org/10.1016/S1470-2045(16)30249-2"},{"label":"LFS Association","url":"https://www.lfsassociation.org/"}],"tags":["gap-fill","hereditary"],"related":["tp53","hereditary-cancer-syndromes","whole-body-mri","adrenocortical","osteosarcoma","rhabdomyosarcoma","medulloblastoma","sarcoma"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["germline-vs-somatic"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-villani-lancet-oncol"],"journals":[],"dependsOn":[],"notes":[],"category":"Genomics & genetics"},"route":"/terms/li-fraumeni/","neighbours":{"target":[{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"term":[{"id":"b-all-cytogenetic-risk","kind":"term","name":"B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)","route":"/terms/b-all-cytogenetic-risk/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"medulloblastoma-molecular-groups","kind":"term","name":"Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)","route":"/terms/medulloblastoma-molecular-groups/"},{"id":"tp53-mutated","kind":"term","name":"TP53-mutated (p53-abnormal)","route":"/terms/tp53-mutated/"}],"technology":[{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","route":"/technologies/whole-body-mri/"}],"cancer":[{"id":"adrenocortical","kind":"cancer","name":"Adrenocortical carcinoma","route":"/cancers/adrenocortical/"},{"id":"choroid-plexus-carcinoma","kind":"cancer","name":"Choroid plexus carcinoma","route":"/cancers/choroid-plexus-carcinoma/"},{"id":"medulloblastoma","kind":"cancer","name":"Medulloblastoma","route":"/cancers/medulloblastoma/"},{"id":"osteosarcoma","kind":"cancer","name":"Osteosarcoma","route":"/cancers/osteosarcoma/"},{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","route":"/cancers/rhabdomyosarcoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"medulloblastoma-shh","kind":"cancer","name":"SHH-activated medulloblastoma","route":"/cancers/medulloblastoma-shh/"}],"paper":[{"id":"paper-villani-lancet-oncol","kind":"paper","name":"Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study","route":"/key-papers/paper-villani-lancet-oncol/"},{"id":"paper-levine-p53-gatekeeper-cell-1997","kind":"paper","name":"Levine 1997: p53, the cellular gatekeeper for growth and division","route":"/key-papers/paper-levine-p53-gatekeeper-cell-1997/"}],"institution":[{"id":"ac-camargo","kind":"institution","name":"A.C. Camargo Cancer Center","route":"/institutions/ac-camargo/"},{"id":"hcpa-porto-alegre","kind":"institution","name":"Hospital de Clínicas de Porto Alegre","route":"/institutions/hcpa-porto-alegre/"},{"id":"sickkids","kind":"institution","name":"The Hospital for Sick Children (SickKids)","route":"/institutions/sickkids/"}],"pathway":[{"id":"p53-mdm2-axis","kind":"pathway","name":"The p53 network (guardian of the genome)","route":"/pathways/p53-mdm2-axis/"}],"biomarker":[{"id":"tp53-del17p","kind":"biomarker","name":"TP53 mutation and del(17p)","route":"/biomarkers/tp53-del17p/"}]}}