A 65-year-old man presents with lytic bone lesions, serum M-spike of 4.2 g/dL (IgG kappa), and plasma cells comprising 30% of the bone marrow. Cytogenetics reveals t(4;14) translocation. Which molecular target is activated by this translocation, and what is its therapeutic relevance?
- A FGFR3 and MMSET are activated; confers bortezomib sensitivity but relative resistance to melphalan
- B FGFR3 and MMSET are activated; associated with high-risk disease and poorer prognosis ✓
- C CCND1 is overexpressed; predicts excellent prognosis with lenalidomide-based therapy
- D MAF is overexpressed; predicts sensitivity to lenalidomide monotherapy
Correct answer: B. FGFR3 and MMSET are activated; associated with high-risk disease and poorer prognosis
Explanation
t(4;14)(p16;q32) juxtaposes the MMSET (NSD2/WHSC1) histone methyltransferase gene and FGFR3 gene with the IGH locus, leading to overexpression of both. This translocation is present in approximately 15% of multiple myeloma cases and is classified as high-risk cytogenetics, associated with inferior outcomes even with modern therapy. t(11;14) dysregulates CCND1 and is standard risk; t(14;16) involves MAF and is also high risk; the question stem specifically tests t(4;14) molecular consequences.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.