Recent studies have shown that molecular events involving the IGH gene at 14q32 are important and initiating events in multiple myeloma (MM).33 Most of the translocations seen in MM are karyotypically silent but readily are identified by FISH studies utilizing molecular probes for 14q32 and its translocation partners. Translocations involving the IGH locus are believed to occur at the time of isotype class switching, in contrast to other B-cell malignancies. Multiple 14q32 translocation partners have been identified in MM, with different prognostic significance. The t(11;14)(q13;q32) translocation involves the cyclin D1 gene in ~25% of MMs and is associated with long survival. The t(4;14)(p16.3;q32) translocation portends the worst prognosis in MM and is seen in ~25% of cases; it involves both the fibroblast growth factor receptor-3 (FGFR3) and MMSET genes at 4p16.3. The t(14;16)(q32;q23) translocation involving the MAF gene conveys an intermediate prognosis, as does the t(6;14)(p25;q32) translocation involving the MUM1/IRF4 gene. The t(14;16) occurs in ~20% of MM. Monosomy 13 is seen in ~50% of MM patients and is associated with an adverse prognosis.
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