In multiple myeloma, the high-risk cytogenetic abnormality associated with the worst prognosis by ISS-R (Revised International Staging System) is:

• A t(11;14) resulting in cyclin D1 overexpression
• B Hyperdiploidy with trisomies of odd-numbered chromosomes
• C t(4;14) with FGFR3 and MMSET overexpression, del17p, or t(14;16) ✓
• D Isolated del13q14 as the sole cytogenetic abnormality

Explanation

R-ISS incorporates cytogenetic risk to refine staging: high-risk cytogenetics include t(4;14), t(14;16), t(14;20), del17p, and gain(1q21). The t(4;14) produces FGFR3-IGH and MMSET (NSD2)-IGH fusions, causing epigenetic dysregulation through H3K36 dimethylation and FGFR3 kinase activation. Del17p causes TP53 haploinsufficiency. t(11;14) and hyperdiploidy are standard-risk and generally favorable; isolated del13q is only adverse in the context of other high-risk features. R-ISS stage III (any ISS III + high-risk cytogenetics or LDH elevation) carries the worst prognosis.

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

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Written and medically reviewed by the StethoPrep medical team.