Characterization of oncogene dysregulation in multiple myeloma by combined FISH and DNA microarray analyses

• Published in: Genes chromosomes & cancer 2005-02, Vol.42 (2), p.117-127
• Main Authors: Fabris, Sonia, Agnelli, Luca, Mattioli, Michela, Baldini, Luca, Ronchetti, Domenica, Morabito, Fortunato, Verdelli, Donata, Nobili, Lucia, Intini, Daniela, Callea, Vincenzo, Stelitano, Caterina, Lombardi, Luigia, Neri, Antonino
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carrier Proteins - genetics; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 14 - genetics; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 20 - genetics; Chromosomes, Human, Pair 4 - genetics; Chromosomes, Human, Pair 6 - genetics; Cyclin D1 - genetics; Cyclin D3; Cyclins - genetics; DNA-Binding Proteins - genetics; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - physiology; Histone-Lysine N-Methyltransferase; Humans; In Situ Hybridization, Fluorescence - methods; Macrophage-Activating Factors - genetics; MafB Transcription Factor; Male; Microarray Analysis - methods; Middle Aged; Multiple Myeloma - genetics; Oncogene Proteins - genetics; Oncogene Proteins, Fusion; Oncogenes - genetics; Protein-Tyrosine Kinases - genetics; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor - genetics; Repressor Proteins - genetics; Transcription Factors - genetics; Translocation, Genetic - genetics
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.20123

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and various partner loci frequently are associated with multiple myeloma (MM). We investigated the expression profiles of the FGFR3/MMSET, CCND1, CCND3, MAF, and MAFB genes, which are involved in t(4;14)(p16.3;q32), t(11;14)(q13;q32), t(6;14)(p21;q32), t(14;16)(q32;q23), and t(14;20)(q32;q12), respectively, in purified plasma cell populations from 39 MMs and six plasma cell leukemias (PCL) by DNA microarray analysis and compared the results with the presence of translocations as assessed by dual‐color FISH or RT‐PCR. A t(4;14) was found in 6 MMs, t(11;14) in 9 MMs and 1 PCL, t(6;14) in 1 MM, t(14;16) in 2 MMs and 1 PCL, and t(14;20) in 1 PCL. In all cases, the translocations were associated with the spiked expression of target genes. Furthermore, gene expression profiling enabled the identification of putative translocations causing dysregulation of CCND1 (1 MM and 1 PCL) and MAFB (1 MM and 1 PCL) without any apparent involvement of immunoglobulin loci. Notably, all of the translocations were mutually exclusive. Markedly increased MMSET expression was found in 1 MM showing associated FGFR3 and MMSET signals on an unidentified chromosome. Our data suggest the importance of using combined molecular cytogenetic and gene expression approaches to detect genetic aberrations in MM. © 2004 Wiley‐Liss, Inc.