Li-Fraumeni Syndrome

Li-Fraumeni Syndrome

• Gene Clinics Entry
• Originally published by Li & Fraumeni in 1969
  • 6 component tumors inherited in an autosomal dominant manner: osteosarcomas, soft-tissue sarcomas, premenopausal breast cancer, brain tumors, adrenal cortical tumors, and acute leukemias
  • Since then, also increased risk of: melanoma, GI (esophagus, stomach, colon/rectum, pancreas), gonadal germ cell tumors, breast cancer/phyllodes tumor, Wilms' tumor, lung, thyroid, GYN (ovary, endometrium, cervix), prostate
• Classic Li-Fraumeni Syndrome (LFS) criteria:
  • A proband with a sarcoma diagnosed before 45 years of age AND
  • A first-degree relative with any cancer under 45 years of age AND
  • A first- or second-degree relative with any cancer under 45 years of age or a sarcoma at any age
• Li-Fraumeni-like Syndrome (LFL) criteria:
  • A proband with any childhood cancer or sarcoma, brain tumor, or adrenal cortical tumor diagnosed before 45 years of age AND
  • A first- or second-degree relative with a typical LFS cancer (sarcoma, breast cancer, brain tumor, adrenal cortical tumor, or leukemia) at any age AND
  • A first- or second-degree relative with any cancer under the age of 60 years
• Cancer risk: ~50% by age 40, 85-90% lifetime
• Approximately 50% have a p53 mutation
• 400 families identified world-wide
• Individuals with LFS/LFL should avoid RT

p53 Mutation

• Classically associated with Li Fraumeni syndrome; approximately 50% of Li Fraumeni patients have p53 mutation
• Associated with a wide spectrum of cancers, including choroid plexus tumors
• "4 core cancers": sarcoma, brain tumor, breast cancer or adrenocorticoid carcinoma before age 50
• PMID 19204208