A 35-year-old man with neurofibromatosis type 2 (NF2) develops bilateral acoustic (vestibular) schwannomas. Which molecular alteration drives schwannoma formation in NF2?
- A Gain-of-function mutation in RAS encoded by NF1 gene on chromosome 17
- B Loss of merlin (schwannomin), a tumour suppressor encoded by NF2 gene on chromosome 22 ✓
- C IDH1/IDH2 mutation causing epigenetic reprogramming
- D BRAF V600E mutation activating the MAPK pathway
Correct answer: B. Loss of merlin (schwannomin), a tumour suppressor encoded by NF2 gene on chromosome 22
Explanation
NF2 encodes merlin (schwannomin), a cytoskeletal tumour suppressor protein on chromosome 22q12. Biallelic loss of merlin causes uncontrolled proliferation of Schwann cells, leading to bilateral vestibular schwannomas — the hallmark of NF2. NF1 mutations (neurofibromin, chromosome 17) cause type 1 neurofibromatosis. IDH mutations characterise diffuse gliomas; BRAF V600E characterises pleomorphic xanthoastrocytoma and papillary craniopharyngioma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.