A 4-year-old girl develops a soft tissue sarcoma of the thigh. Her father had osteosarcoma at age 30, and a paternal aunt died of adrenocortical carcinoma in childhood. Germline testing of this child is most likely to reveal a mutation in which gene?
- A RB1
- B TP53 ✓
- C APC
- D BRCA1
Correct answer: B. TP53
Explanation
This pedigree defines Li-Fraumeni syndrome, caused by germline TP53 mutation, characterized by early-onset sarcomas (osteosarcoma, soft tissue sarcoma), breast cancer, adrenocortical carcinoma, leukemia, and brain tumors occurring at unusually young ages. Germline RB1 mutation causes hereditary retinoblastoma and secondarily osteosarcoma, but retinoblastoma and the specific clustering here point to TP53. APC causes familial adenomatous polyposis and BRCA1 causes hereditary breast and ovarian cancer, neither matching this pattern.
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.