A 70-year-old man with multiple myeloma undergoes bone marrow biopsy. FISH shows t(4;14)(p16;q32) involving FGFR3 and MMSET (NSD2). This translocation is associated with which prognostic and treatment-relevant feature?
- A Standard-risk disease; associated with cyclin D1 overexpression via IgH enhancer
- B Low-risk disease; associated with trisomies of odd-numbered chromosomes (hyperdiploid myeloma)
- C High-risk disease; associated with overexpression of MMSET causing histone H3K36 methylation and global epigenetic reprogramming ✓
- D Standard risk; associated with MAF transcription factor overexpression causing cyclin D2 upregulation
Explanation
t(4;14) juxtaposes FGFR3 (fibroblast growth factor receptor 3) and MMSET (NSD2, a histone H3K36 methyltransferase) with the IgH locus enhancer. MMSET overexpression drives a permissive epigenetic state with global H3K36 dimethylation, enhancing gene transcription across the myeloma genome. t(4;14) is classified as high-risk myeloma in the Revised ISS (R-ISS) and IMWG risk stratification systems. Standard-risk translocations include t(11;14) causing cyclin D1 overexpression. Hyperdiploid myeloma with trisomies is considered standard/low risk. t(14;16) and t(14;20) involve MAF proteins and confer high risk.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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Written and medically reviewed by the StethoPrep medical team.