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Diagnostic evaluation of t(4;14) in multiple myeloma and evidence for clonal evolution

Leukemia volume 21, pages 2358–2359 (2007)Cite this article

The presence of a t(4;14) in multiple myeloma (MM) is associated with significantly inferior outcomes following both conventional chemotherapy and high-dose melphalan-based treatment regimens.1, 2 Detection of patients bearing the t(4;14) is therefore important in an MM molecular workup. Furthermore, since targeted inhibitors of the associated fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase are now in clinical trials,3 detection of MM patients who express the FGFR3 protein is also of potential therapeutic relevance. With this in mind, we have employed the infrastructure of the Multiple Myeloma Research Consortium (MMRC) tissue bank to evaluate four different methodologies for the molecular diagnostic detection of this translocation. The methods employed are published previously4, 5, 6 or are provided as Supplementary Information.

Fresh bone marrow samples were collected in a uniform fashion from 84 patients with active MM. Immunocytochemistry (ICC)4 and flow cytometry for FGFR3 were performed on fresh samples at the retrieval site, while split samples were then shipped by overnight courier to the MMRC central laboratory, where they were processed according to standard operating procedures, under good laboratory practice (GLP) conditions. Processed samples were then analyzed for detection of the t(4;14) by both IgH-MMSET polymerase chain reaction (PCR)5 – on blood and bone marrow mononuclear cells – and dual fusion cytoplasmic immunoglobulin fluorescence in situ hybridization (cIg-FISH) of bone marrow using a commercially available probe for the t(4;14) (Vysis Inc., DesPlaines, IL, USA).6

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References

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Acknowledgements

This work was supported by the Multiple Myeloma Research Consortium and Multiple Myeloma Research Foundation.

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Authors and Affiliations

  1. Division of Hematology – Oncology, Mayo Clinic College of Medicine, Scottsdale, AZ, USA

    A K Stewart, J Keats, S Van Wier, G Ahmann, T Price-Troska, P L Bergsagel, M Chesi & R Fonseca

  2. Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada

    H Chang, S Trudel, D Reece & Z Li

  3. Department of Hematology – Oncology, Dana Farber Cancer Institute, Boston, MA, USA

    K C Anderson & P Richardson

  4. Division of Hematology–Oncology, Moffit Cancer Center, Tampa, FL, USA

    M Alsina

  5. Multiple Myeloma Research Consortium, New Caanan, CT, USA

    S Young, A Sable-Hunt & K Giusti

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  1. A K Stewart
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  2. H Chang
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  3. S Trudel
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  4. K C Anderson
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  6. M Alsina
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  7. D Reece
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  8. S Young
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  9. A Sable-Hunt
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  10. Z Li
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  11. J Keats
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  12. S Van Wier
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  13. G Ahmann
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  14. T Price-Troska
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  15. K Giusti
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  16. P L Bergsagel
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  17. M Chesi
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  18. R Fonseca
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Corresponding author

Correspondence to A K Stewart.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Stewart, A., Chang, H., Trudel, S. et al. Diagnostic evaluation of t(4;14) in multiple myeloma and evidence for clonal evolution. Leukemia 21, 2358–2359 (2007). https://doi.org/10.1038/sj.leu.2404800

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