A 45-year-old woman with MEN1 syndrome has a pancreatic neuroendocrine tumor. Which tumor suppressor gene on chromosome 11q13 is most likely mutated and is required for MEN1-associated tumor development according to Knudson's two-hit hypothesis?

• A MENIN (MEN1) ✓
• B RB1
• C TP53
• D CDKN2A

Explanation

MEN1 syndrome is caused by germline mutations in the MENIN gene (MEN1) located on chromosome 11q13. MENIN is a tumor suppressor that functions as part of a histone methyltransferase complex (MLL/SET1 complex) regulating transcription via H3K4 methylation. Pancreatic NETs in MEN1 require biallelic inactivation (two-hit): the inherited germline mutation plus somatic LOH at 11q13. RB1 is on 13q14 and governs retinoblastoma/osteosarcoma; TP53 mutations are common in sporadic cancers but are not the MEN1 mechanism; CDKN2A encodes p16/p14ARF relevant to melanoma predisposition.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.