Li-Fraumeni Syndrome (TP53)

A 28-year-old woman presents with a diagnosis of invasive ductal carcinoma of the breast. Her mother died of osteosarcoma at age 19, and her maternal grandmother had gastric cancer at age 42. Genetic testing reveals a germline missense mutation in the TP53 gene located on the region marked **B** in the diagram. Which of the following best explains the molecular mechanism underlying the high cancer predisposition in this family?