A 17-year-old boy undergoing screening colonoscopy for familial polyposis presents with hundreds of adenomatous polyps throughout the colon. Vital signs are normal (BP 118/76, HR 72, RR 16, Temp 37°C). His father underwent colectomy in his twenties for identical pathology. Laboratory studies show normal hemoglobin and no occult blood in stool currently. Which molecular abnormality most likely initiates the earliest step in his polyp development?
- A)Inactivation of VHL with increased HIF activity
- B)Loss of APC leading to accumulation of beta cateninGABARITO
- C)Amplification of HER2 on chromosome 17
- D)Activation of BCL2 preventing apoptosis
- E)Mutation of JAK2 causing constitutive tyrosine kinase activity
Explicação
Familial adenomatous polyposis is caused by germline loss of APC, a tumor suppressor that normally helps degrade beta catenin. Without APC, beta catenin accumulates and drives transcription of proliferative genes, initiating the adenoma sequence in the colon. Ver explicação completa e trilha adaptativa →