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IGH/CCND3 Plus Translocation, Dual Fusion

Applications
haematology
Catalogue Numbers
LPH 075-S (5 tests)
LPH 075 (10 tests)

Probe Specification

  • CCND3, 6p21, Red
  • IGH, 14q32.33, Green

The IGH/CCND3 Plus product consists of probes labelled in green, proximal to the Constant, and within the Variable segment of the IGH region and CCND3 probes, labelled in red. The CCND3 probe mix contains a 158kb probe telomeric to the CCND3 gene, including the D6S1017 marker and a second probe covering the 244kb region centromeric to the TAF8 gene, including the D6S400 and the D6S1463 markers.

Probe Information

The CCND3 (cyclin D3) gene is located at 6p21.1 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(6;14)(p21;q32) translocation is a recurrent translocation seen in 4% of cases of MM2.

CCND3 has been identified as a putative oncogene that is dysregulated as a consequence of the t(6;14)(p21;q32) translocation2. The translocation appears to be mediated by an error in IgH switch recombination as it has been shown that in KMM-1 cell lines, the translocation disrupts a switch sequence in this region and results in juxtaposition of CCND3 with the IGH promoter, thus elevating the levels of CCND3 expression2. It is thought that this mechanism is similar in all cases of IGH translocation. Most breakpoints appear to be clustered in a region that is fewer than 200kb centromeric to CCND32.

CCND3-IGH translocations are also reported in a variety of other B-cell malignancies, including plasma cell leukaemia, diffuse large B-cell lymphoma (DLBCL) and splenic lymphoma with villous lymphocytes (SLVL)3.

I first came across Cytocell FISH probes in a previous lab I worked in and I was struck by the quality of the products. Since this time, I have been recommending and introducing Cytocell probes across all application areas — now they are the primary FISH probes used in our lab. They have an excellent range of products and their ready-to-use reagent format saves considerable time. As a matter of fact, at a recent conference there was a discussion about the lack of commercial probes for a particular disorder and I was happy to point the participants in the direction of the Cytocell catalogue, which contains the exact probes required. Elizabeth Benner, Medical Technologist at the University of Arizona Health Network 

References

  1. Fonseca et al., Cancer Res 2004;64:1546-58
  2. Shaughnessy et al., Blood 2001;98(1):217-23
  3. Soniki et al., Blood 2001;98(9):2837-44
  4. Arsham, MS., Barch, MJ. and Lawce HJ. (eds.) (2017) The AGT Cytogenetics Laboratory Manual. New Jersey: John Wiley & Sons Inc.
  5. 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.
  6. 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 CCND3 Plus Translocation Dual Fusion magnified
Area of Interest*
Lymphoma

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.