title: Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease.
abstract: To investigate the patterns of genetic lesions in a panel of 23 human multiple myeloma cell lines (HMCLs), we made a genomic integrative analysis involving FISH, and both gene expression and genome-wide profiling approaches. The expression profiles of the genes targeted by the main IGH translocations showed that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different levels in all of the HMCLs, and that the expression of the MAF gene was not restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses identified a limited number of genes specifically associated with t(4;14) and involved in different biological processes. The signature related to MAF/MAFB expression included the known MAF target genes CCND2 and ITGB7, as well as genes controlling cell shape and cell adhesion. Genome-wide DNA profiling allowed the identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines, together with recurrent gains on 8q, 18q, 7q, and 20q; the most frequent deletions affected 1p, 13q, 17p, and 14q; and almost all of the cell lines presented LOH on chromosome 13. Two hundred and twenty-two genes were found to be simultaneously overexpressed and amplified in our panel, including the BCL2 locus at 18q21.33. Our data further support the evidence of the genomic complexity of multiple myeloma and reinforce the role of an integrated genomic approach in improving our understanding of the molecular pathogenesis of the disease. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
authors.affiliation: Centro di Genetica Molecolare ed Espressione Genica, Fondazione IRCCS Policlinico, Milan, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Lombardi
authors.forename: Giulia
authors.initials: G
authors.lastname: Poretti
authors.forename: Michela
authors.initials: M
authors.lastname: Mattioli
authors.forename: Sonia
authors.initials: S
authors.lastname: Fabris
authors.forename: Luca
authors.initials: L
authors.lastname: Agnelli
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Ivo
authors.initials: I
authors.lastname: Kwee
authors.forename: Andrea
authors.initials: A
authors.lastname: Rinaldi
authors.forename: Domenica
authors.initials: D
authors.lastname: Ronchetti
authors.forename: Donata
authors.initials: D
authors.lastname: Verdelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lambertenghi-Deliliers
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertoni
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D018628:Gene Dosage; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495607:MAF protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051257:Proto-Oncogene Proteins c-maf