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 FGFR3 (fibroblast growth factor receptor 3) gene is located at 4p16.3 and IGH (immunoglobulin heavy locus) at 14q32.33.
Approximately 50-60% of multiple myeloma (MM) cases are associated with translocations involving IGH and one of several partners including CCND1, NSD2 (MMSET) and FGFR3, CCND3, MAF or MAFB1.
The t(4;14)(p16.3;q32.3) translocation is a recurrent translocation seen in 15% of MMs2,3.
The translocation results in the dysregulation of two genes at 4p16; NSD2 (nuclear receptor binding SET domain protein 2) and FGFR3. The consequence of the translocation is increased expression of FGFR3 and NSD2. The translocation can be unbalanced, with 25% of cases losing the derivative chromosome 14, associated with the loss of FGFR3 expression2,3.
The majority of the breakpoints on chromosome 4 occur between FGFR3 and NSD2. The breakpoint on chromosome 14 is almost exclusively in the switch region of constant genes. For the overexpression of both FGFR3 and NSD2 the breakpoint on chromosome 14 must be located between the μ enhancer and the 3’ IGH enhancers and between FGFR3 and NSD2. As a consequence, both derivative chromosomes contain an enhancer juxtaposed to an oncogene4.
This t(4;14) translocation is often cytogenetically cryptic and was poorly described before the advent of FISH techniques. The translocation has been associated with poorer survival in MM patients2, 3.
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
- Fonseca et al., Cancer Res 2004;64:1546-58
- Fonseca et al., Leukemia 2009;23(12):2210-2221
- Sawyer, Cancer Genetics 2011;204(1):3-12
- Walker et al., Blood 2013;121(17);3413-3419
- Arsham, MS., Barch, MJ. and Lawce HJ. (eds.) (2017) The AGT Cytogenetics Laboratory Manual. New Jersey: John Wiley & Sons Inc.
- Mascarello JT, Hirsch B, Kearney HM, et al. Section E9 of the American College of Medical Genetics technical standards and guidelines: fluorescence in situ hybridization. Genet Med. 2011;13(7):667-675.
- Wiktor AE, Dyke DLV, Stupca PJ, Ketterling RP, Thorland EC, Shearer BM, Fink SR, Stockero KJ, Majorowicz JR, Dewald GW. Preclinical validation of fluorescence in situ hybridization assays for clinical practice. Genetics in Medicine. 2006;8(1):16–23.
- 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.