Dysregulation of FGFR3 and MMSET by t(4;14)(p16.3;q32) in multiple myeloma.

A) The relative positions of the FGFR3 and MMSET genes, both of which are dysregulated by the t(4;14) translocation, are depicted on chromosome 4p16.3, near the telomere. Similarly, the organization of the IgH locus, including the intronic enhancer (Em) and the 3′ enhancer (3′E), are depicted at 14q32 near the telomere. The arrows indicate the transcriptional orientation of the MMSET gene and the IgH locus, both toward the centromere.

B) A translocation into switch regions (a hybrid mu/gamma switch region in this case) separates the two enhancers. The more telomeric Em segregates to der(4), dysregulating MMSET. The telomeric region of chromosome 4, containing FGFR3, segregates to der(14), where it is dysregulated by the powerful influence of the 3′ E. Promoter sites (P) are noted, with the size of the arrowhead indicating the direction and amount of transcription. Exons are represented by boxes, that are joined by RNA splicing as indicated by thin lines. See text for additional details.