Li-Fraumeni syndrome

First reported in 1969 by Frederick Li & Joseph Fraumeni from the National Cancer Institute. Epidemiology: - rare, 1 in 5000-20,000 families - early age of the cancer diagnosis with ~1/2 of affected individuals diagnosed with cancer < 30 years of age Pathology: 1) so-called SBLA tumors - sarcoma, breast, bone, brain, lung, larynx, leukemia liver & adrenal cortex tumors 2) mutated p53 has longer 1/2life than normal p53 - tumors stain positively for p53 Genetics: - p53 chromosomal aberrations autosomal dominant (70% of families) - 25% with sporadic p53 mutations - CHEK2 chromosomal aberrations - cancer risk in carriers of CHEK2 mutation may be far less than p53 mutation - associated with defects in CDKN2A Laboratory: - TP53 gene mutation - CHEK2 gene mutation - complete blood count (CBC) every 4 months for leukemia or lymphoma - erythrocyte sedimentation rate & serum lactate dehydrogenase every 4 months [3] Diagnostic criteria: - sarcoma diagnosed < 45 years of age - 1st degree relative with any cancer < 45 years of age - 1st degree or 2nd degree relative with any cancer < 45 years of age [3] - other criteria & criteria for Li-Fraumeni-like syndrome [3] Special laboratory: - colon cancer: - colonoscopy very 2 years, beginning at age 25-30 or 10 years before the earliest known colon cancer in the family [3] Radiology: - breast MRI & clinical breast examination twice a year, starting at age 20 to 25, or 5 to 10 years before the earliest known breast cancer diagnosis in the family - brain tumor: annual brain MRI - soft tissue & bone sarcoma: - annual whole-body MRI - ultrasound of abdomen & pelvis every 6 months [3] * a TP53 genetic mutation can cause a person to have an increased sensitivity to therapeutic (ionizing) radiation - if possible, people with a germline TP53 mutation should avoid or minimize exposure to diagnostic radiation [3] Management: - annual dermatology (skin) examination for melanoma

Related

breast cancer cellular tumor antigen p53; tumor suppressor p53, phosphoprotein p53; antigen NY-CO-13 (TP53, p53) checkpoint kinase 2; serine/threonine protein kinase Chk2; homolog of S. cerevisiae Rad53; Cds1 (CHEK2, CHK2, RAD53) Li-Fraumeni syndrome genotyping

Specific

Li Fraumeni syndrome 2 (CHK2 mutation associated) Li Fraumeni syndrome/TP53 mutation associated

Properties

ASSOCIATED-NEOPLASM[S]: breast cancer glial neoplasm (glioma) sarcoma :SITE soft tissue adenocarcinoma of the lung osteosarcoma melanoma osteosarcoma leukemia lymphoma adrenal cortical carcinoma pancreatic adenocarcinoma prostate cancer