About this condition
TP53 & Li-Fraumeni Syndrome
TP53 is the most commonly mutated gene in human cancer (somatic). Germline TP53 mutations cause Li-Fraumeni syndrome (LFS), affecting ~1 in 5,000-20,000 individuals. LFS confers lifetime cancer risk approaching 100% — ~50% by age 30 and >90% by age 70. Core tumors: premenopausal breast cancer, soft tissue sarcomas, osteosarcoma, brain tumors (gliomas, choroid plexus carcinoma), adrenocortical carcinoma (ACC), and leukemia.
Surveillance: annual whole-body MRI (Toronto protocol), breast MRI every 6 months from age 20, annual brain MRI, abdominal ultrasound every 3-4 months for children (ACC detection), colonoscopy every 2-5 years. The Toronto protocol improves survival by detecting cancers at earlier, more treatable stages.
Radiation therapy should be AVOIDED in LFS carriers — TP53-deficient cells have impaired DNA damage repair, increasing secondary cancer risk. Mastectomy preferred over lumpectomy+radiation for LFS breast cancer. Proton beam preferred over photon radiation when radiation cannot be avoided.
Childhood adrenocortical carcinoma is nearly pathognomonic for LFS — 50-80% carry germline TP53 mutations. Any child with ACC should have TP53 testing regardless of family history.
- Gene locus
- TP53 (17p13.1)
