Molecular profiles associated with cyclins D dysregulation and IGH translocations in multiple myeloma

Introduction: The deregulation of CCND1, CCND2 and CCND3 genes may represent a unifying oncogenic event in multiple myeloma (MM), being at least one of them deregulated in almost all MM tumors. A recent classification (TC classification) grouped MM patients into 5 classes on the basis of the Cyclin D expression profiles and the presence of the main translocations involving the immunoglobulin heavy chain locus (IGH) at 14q32.Methods: The gene expression profiles of purified plasma cells from 50 MM cases were used to stratify the samples into the 5 five TC classes and to identify the transcriptional fingerprints of these subgroups. Cyclins D expression data were validated by Q-RT-PCR analysis; FISH was used to investigate Cyclin D loci arrangement, to detect the main IGH translocations and the chromosome 13q deletion. Results: 110 probe set were identified by class-prediction analysis as characterizing TC1, TC2, TC4 and TC5 groups, while TC3 samples showed a heterogeneous phenotype and no marker gene. TC2 group, showing the presence of extracopies of CCND1 locus, was characterized by the overexpression of genes involved in protein biosynthesis at the translational level. A meta-analysis on published datasets validated the identified expression signatures. Conclusions: Our data provide contributions to the understanding of the molecular and biological features of distinct subtypes of MM. The identification of distinctive patterns of gene expression associated with TC2 patients may improve the risk stratification and indicate novel therapeutic targets.