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A TC classification-based predictor for multiple myeloma using multiplexed real-time quantitative PCR

Leukemia volume 27, pages 1754–1757 (2013)Cite this article

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The recurrent IGH translocations in myeloma define biologically important subgroups of disease that are not only associated with prognosis, but are also characterised by the unique overexpression of potentially targetable proteins.1, 2, 3, 4 Inhibitors of MMSET or FGFR3, both overexpressed in t(4;14) myeloma, or MEK kinase inhibitors, targeting downstream effectors of MAF in cases with t(14;16), are currently under development.5, 6, 7 Thus, identifying these translocation groups in the clinic will become essential for a personalised treatment approach. Expression of a translocation target gene together with the expression of a D group cyclin has been used as a disease classifier for myeloma (TC classification).1, 8 Here, we have developed a novel test for the detection of the TC groups using multiplexed real-time quantitative reverse transcriptase-PCR (qRT-PCR). The assay assesses the expression of the translocation target genes FGFR3 and MMSET (overexpressed in t(4;14)), CCND1 (overexpressed in t(11;14)), MAF (overexpressed in t(14;16)), MAFB (overexpressed in t(14;20)), ITGB7 and CX3CR1 (overexpressed in t(14;16) and t(14;20)), CCND3 (overexpressed in t(6;14)), CCND2 (overexpressed secondary to MAF/MAFB), CKS1B (amplified in gain(1q)), relative to the housekeeping gene GAPDH in five parallel real-time PCR reactions. The test is designed to run on a standard real-time PCR cycler using standard reagents (Supplementary Methods).

The assay was validated in 255 presentation bone marrow myeloma samples from patients treated in the MRC Myeloma IX trial.9 Sorting of myeloma cells, methods of RNA isolation and cDNA synthesis were performed following standard protocols. Interphase fluorescence in situ hybridisation (FISH) data were available for all patients. Details regarding the Myeloma IX trial, patient characteristics and sample processing can be found in Supplementary Methods.

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Acknowledgements

MFK is funded by the Deutsche Forschungsgemeinschaft (KA 3338/1-1). BAW and CPW are funded by Myeloma UK. We also gratefully acknowledge funding from the National Institute of Health Biomedical Research Centre at the Royal Marsden Hospital.

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Authors and Affiliations

  1. Division of Molecular Pathology, Haemato-Oncology Research Unit, The Institute of Cancer Research, London, UK

    M F Kaiser, B A Walker, S L Hockley, D B Begum, C P Wardell, D Gonzalez, F E Davies & G J Morgan

  2. Department of Haematology and Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany

    M F Kaiser

  3. Wessex Regional Genetics Laboratory, University of Southampton, Salisbury, UK

    F M Ross

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  1. M F Kaiser
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  2. B A Walker
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Correspondence to G J Morgan.

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Supplementary Information accompanies the paper on the Leukemia website

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Kaiser, M., Walker, B., Hockley, S. et al. A TC classification-based predictor for multiple myeloma using multiplexed real-time quantitative PCR. Leukemia 27, 1754–1757 (2013). https://doi.org/10.1038/leu.2013.12

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