A 7-year-old girl is diagnosed with rhabdomyosarcoma. Family history reveals her father had osteosarcoma at age 12 and her aunt died of breast cancer at 33. Genetic counseling identifies a germline mutation in a tumor suppressor gene encoding a transcription factor that regulates cell cycle checkpoints and apoptosis. The mutated gene is:
- A RB1
- B APC
- C TP53 ✓
- D BRCA2
Correct answer: C. TP53
Explanation
Li-Fraumeni syndrome arises from germline TP53 mutation and predisposes to diverse malignancies at unusually young ages, classically sarcomas, breast cancer, leukemia, adrenocortical carcinoma and brain tumors, often with multiple primaries in one individual. p53 acts as a guardian of the genome, halting the cycle after DNA damage and triggering apoptosis if repair fails. RB1 predisposes mainly to retinoblastoma and osteosarcoma, not this spectrum.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.