There are five well-defined recurrent chromosomal partners (oncogenes) that are involved in IgH translocations in MGUS and MM: 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (FGFR3 and MMSET), 16q23 (c-maf) and 20q11 (mafB). The combined prevalence of these five IgH translocation partners is about 40%, with approximately 15% 11q13, 3% 6p21, 15% 4p16, 5% 16q23 and 2% 20q11. The t(4;14) translocation is unusual in that it appears to dysregulate two potential onco-genes, MMSET on der(4), and FGFR3 on der(14), although FGFR3 on der(14) is lost or not expressed in about 20% of MM tumors that have a t(4;14) translocation. The apparently lower incidence of 4p16 and/or 16q23 in MGUS/smoldering MM compared with MM may be due to these translocations resulting in de novo MM without preceding MGUS, or a more rapid progression of MGUS to MM, an hypothesis supported by the fact that patients with translocations involving 4p16 or 16q23 have an extremely poor prognosis.
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