Chromosome 4p

t(4;14)(p16;q32) is present in about 15% of myeloma patients and 2-6% of patients with MGUS.44,45 It is detectable only by molecular cytogenetics due to its extreme telomeric position. Consequent to this translocation, FGFR3 (fibroblast growth factor receptor 3) from der(14) and MMSET from der(4) localized in the breakpoint regions are overexpressed.46 47 FGFR3 is a member of fibroblast growth factor receptor tyrosine kinases. Its mutation is shown to cause constitutive activation of the receptor in neonatal thanatropic dysplasia.48 Similarly, in myeloma with t(4;14), it is constitutively activated.47

The second putative oncogene in t(4;14) is MMSET/WHSC1. It is a candidate gene for a multiple malformation syndrome known as Wolf-Hirschhorn syndrome. Among myeloma patients with t(4;14), approximately 32% lack FGFR3 expression, yet express MMSET, supporting its role in oncogenesis.49,50

The t(4;14) has been shown to confer a poor prognosis. Fonseca et al.33 reported that patients in whom this translocation had been identified, using cIg-FISH, had a significantly shorter survival (26 months vs 45 months). However, Rasmussen et al. did not find any correlation between outcome and FGFR3 overexpres-sion,51 and FGFR3 overexpression was identified in only 74% of patients with t(4;14) by Keats et al.50 In the latter study, t(4;14) predicted poor survival, irrespective of FGFR3 expression.

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