A patient with plasma cell myeloma undergoes cytogenetics. FISH reveals t(4;14)(p16.3;q32). This translocation juxtaposes FGFR3 and MMSET (NSD2) to the IGH locus. The prognostic significance and therapeutic implication is:
- A Favorable prognosis; responds best to thalidomide-based regimens
- B High-risk; FGFR3 overexpression may respond to FGFR inhibitors in FGFR3-expressing cases ✓
- C Standard risk; no targeted therapy available, standard ASCT recommended
- D High-risk but responds exceptionally to lenalidomide, making it low-risk with treatment
Correct answer: B. High-risk; FGFR3 overexpression may respond to FGFR inhibitors in FGFR3-expressing cases
Explanation
t(4;14) is a high-risk cytogenetic abnormality in myeloma, associated with shorter PFS and OS even with modern therapies. It juxtaposes both FGFR3 (on 4p16.3) and NSD2/MMSET (histone methyltransferase) to IGH; MMSET overexpression is universal, while FGFR3 is expressed in ~75% of cases. FGFR3 overexpression is a targetable alteration with selective FGFR inhibitors. Unlike del(17p) and t(14;16), t(4;14) patients show partial benefit from bortezomib-based therapy.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.