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IGH/FGFR3 Plus Translocation, Dual Fusion

Applications
haematology
Catalogue Numbers
LPH 074-S (5 tests)
LPH 074 (10 tests)

Probe Specification

  • FGFR3, 4p16.3, Red
  • IGH, 14q32.33, Green

The IGH/FGFR3 Plus product consists of probes, labelled in green, proximal to the Constant, and within the Variable segment of the IGH region 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.

Probe Information

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 (WHSC1) 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; WHSC1 (Wolf-Hirschhorn syndrome candidate 1) and FGFR3. The consequence of the translocation is increased expression of FGFR3 and WHSC1. 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 WHSC1. The breakpoint on chromosome 14 is almost exclusively in the switch region of constant genes. For the overexpression of both FGFR3 and WHSC1 the breakpoint on chromosome 14 must be located between the μ enhancer and the 3’IGH enhancers and between FGFR3 and WHSC1. 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.

In our hands, Cytocell FISH probes, have proven to be of the highest quality with bright, easy to interpret signals, thus providing confidence in our results. Cytocell’s customer support is outstanding, as their staff are extremely knowledgeable and truly care about their customers and their customers’ needs. Jennie Thurston, Director of Cytogenetics at Carolinas Pathology Group

References

  1. Fonseca et al., Cancer Res 2004;64:1546-58
  2. Fonseca et al., Leukemia 2009;23(12):2210-2221
  3. Sawyer, Cancer Genetics 2011;204(1):3-12
  4. Walker et al., Blood 2013;121(17);3413-3419
  5. Arsham, MS., Barch, MJ. and Lawce HJ. (eds.) (2017) The AGT Cytogenetics Laboratory Manual. New Jersey: John Wiley & Sons Inc.
  6. 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.
  7. 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.

Microscope Images

IGH FGFR3 Plus Translocation Dual Fusion magnified
Area of Interest*
MM

Disclaimer

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.