Define Li-Fraumeni syndrome, the gene implicated, and the cancer risks that prompt surveillance strategies.

• A. Li-Fraumeni is caused by germline TP53 mutations and predisposes to a broad spectrum of early-onset cancers including sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma, necessitating intensive surveillance.
• B. Li-Fraumeni is caused by BRCA2 mutations; only breast cancer risk.
• C. Li-Fraumeni is caused by MLH1 mutations; colorectal cancer risk.
• D. Li-Fraumeni is caused by APC mutations; polyposis.

Answer: (A)

Li-Fraumeni syndrome is a hereditary cancer predisposition caused by germline mutations in TP53, the gene encoding the p53 tumor suppressor that acts as a guardian of the genome. When TP53 is altered in every cell, the risk of developing cancer is dramatically increased and tends to appear at a younger age, with a characteristic broad spectrum of possible tumors. The cancers that drive the need for proactive surveillance include sarcomas (especially in childhood), premenopausal breast cancer, brain tumors, and adrenocortical carcinoma; this combination is a key reason clinicians implement intensive, lifelong surveillance for individuals with this syndrome. Because p53-deficient cells are more sensitive to DNA damage from radiation, surveillance programs emphasize minimizing ionizing radiation and favor noninvasive imaging when possible. As a result, strategies often use regular whole-body MRI and brain MRI, with breast cancer screening initiated earlier and tailored every step of the way to catch cancers early while reducing radiation exposure.

The other options mix up the syndrome with different genes and cancer patterns (BRCA2 is linked mainly to breast/ovarian cancer risk, MLH1 to Lynch colorectal cancer, APC to polyposis), which is why they don’t fit Li-Fraumeni.