Multiple myeloma (MM) is a clonal B-cell disorder characterized by malignant proliferation of monoclonal plasma cells. MM cases present a common histological and morphological diagnosis, but enormous genetic and molecular complexity as well as marked variations in clinical characteristics and in patient survival. Recent progress in molecular cytogenetics has improved our understanding of the pathogenesis of MM and has also provided reasoning for molecular sub-classification of MM. MLPA has been shown to be a reliable technique to detect copy number alterations in MM (Alpar D. et al. 2013 and Boyle EM. et al. 2014). As balanced translocations also have a high importance in the prognostic classification of MM patients, MLPA and i-FISH are suggested to be applied as complimentary techniques in this entity.
This P425-B2 Multiple Myeloma probemix contains a total of 46 probes for the following chromosomal regions and target genes: 1p32-p12, 1q21-q23, 5q31, chr. 9, 12p13, 13q14-q22 (RB1-DLEU2-DIS3), 14q32 (TRAF3), chr. 15, 16q12-q23 (CYLD-WWOX) and 17p13 (TP53). These regions and genes are suggested to be of prognostic relevance in MM. In addition, 11 reference probes have been included in this probemix, detecting different autosomal chromosomal locations which have a relatively stable copy number in MM.
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the above mentioned chromosomal regions in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.