# Li-Fraumeni syndrome (germline TP53)

Source: https://onco.cc/terms/li-fraumeni/  
OnCo record `li-fraumeni` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-08
- Tags: gap-fill; hereditary

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Li–Fraumeni_syndrome
- Toronto protocol (Lancet Oncol 2016): https://doi.org/10.1016/S1470-2045(16)30249-2
- LFS Association: https://www.lfsassociation.org/

## Connected records

- targets: [TP53](https://onco.cc/targets/tp53/)
- terms: [B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)](https://onco.cc/terms/b-all-cytogenetic-risk/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)](https://onco.cc/terms/medulloblastoma-molecular-groups/), [TP53-mutated (p53-abnormal)](https://onco.cc/terms/tp53-mutated/)
- technologies: [Whole-body MRI](https://onco.cc/technologies/whole-body-mri/)
- cancers: [Adrenocortical carcinoma](https://onco.cc/cancers/adrenocortical/), [Choroid plexus carcinoma](https://onco.cc/cancers/choroid-plexus-carcinoma/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [Osteosarcoma](https://onco.cc/cancers/osteosarcoma/), [Rhabdomyosarcoma](https://onco.cc/cancers/rhabdomyosarcoma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [SHH-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-shh/)
- key papers: [Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study](https://onco.cc/key-papers/paper-villani-lancet-oncol/), [Levine 1997: p53, the cellular gatekeeper for growth and division](https://onco.cc/key-papers/paper-levine-p53-gatekeeper-cell-1997/)
- institutions: [A.C. Camargo Cancer Center](https://onco.cc/institutions/ac-camargo/), [Hospital de Clínicas de Porto Alegre](https://onco.cc/institutions/hcpa-porto-alegre/), [The Hospital for Sick Children (SickKids)](https://onco.cc/institutions/sickkids/)
- pathways: [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/)
- biomarkers: [TP53 mutation and del(17p)](https://onco.cc/biomarkers/tp53-del17p/)

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