Radiation Oncology/Cancer Syndromes/Li-Fraumeni

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