IGH/FGFR3 Translocation, Dual Fusion
- FGFR3, 4p16.3, Red
- IGH, 14q32.33, Green
The IGH/FGFR3 product consists of probes, labelled in green, covering the Constant, J, D and Variable segments of the IGH gene, and FGFR3 probes, labelled in red. The FGFR3 probe mix contains a 118kb probe telomeric to FGFR3, including the D4S2561E marker and a second probe covering the 126kb region centromeric to MMSET, including the D4S1182 marker.
The t(4;14)(p16.3;q32.3) translocation is found in 15-20% of multiple myeloma patients and results in the known dysregulation of two genes, one on each derivative chromosome: MMSET (Multiple Myeloma SET domain containing protein, also known as WHSC1) on the der(4) and FGFR3 (fibroblast growth factor receptor 3) on the der(14)1.
The majority of the breakpoints on chromosome 4 occur within the MMSET locus resulting in a fusion gene where the 5' exons of MMSET are replaced with the VDJ region of the heavy chain locus. This results in MMSET being brought under the influence of the enhancer EÂµ on the der(4)1, FGFR3 lies at least 50kb from the breakpoints after translocation to chromosome 14 and FGFR3 expression is upregulated via proximity to the strong enhancer elements (particularly the Ea enhancer) in the immunoglobulin heavy chain2. Other studies state that the breakpoints on chromosome 4 lie in a 113kb region between FGFR3 and MMSET exon 53.
The breakpoint on chromosome 14 is almost exclusively in or near the switch region of the IGH locus. This t(4;14) translocation is often cytogenetically cryptic and was poorly described before the advent of FISH techniques.
I am grateful for the excellent products I receive from Cytocell at a reasonable price, but more importantly the superb customer support. The speed in which I receive answers or suggestions makes my life as a director much easier and allows me to focus on patient care. The quality and consistency of Cytocell’s probes means I can trust the results, and my clients get their results in a timely manner. Dr. Theresa C. Brown, Director, Cytogenetics Laboratory, Hayward Genetics Center, Tulane University School of Medicine
1. Viguié F t(4;14)(p16;q32). Atlas Genet Cytogenet Oncol Haematol. May 20052.
2. Sibley K et al., Oncogene. 2001 Feb 8;20(6):686-913.
3. Keats JJ et al., Blood 2003;101(4):1520-9
- Area of Interest*
This product is intended to be used on Carnoy’s solution (3:1 methanol/acetic acid) fixed haematological samples.
*Disease information supported by the literature and is not a reflection of the intended purpose of this product.