Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease.
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.
Lombardi
Luigia
L
Centro di Genetica Molecolare ed Espressione Genica, Fondazione IRCCS Policlinico, Milan, Italy.
Poretti
Giulia
G
Mattioli
Michela
M
Fabris
Sonia
S
Agnelli
Luca
L
Bicciato
Silvio
S
Kwee
Ivo
I
Rinaldi
Andrea
A
Ronchetti
Domenica
D
Verdelli
Donata
D
Lambertenghi-Deliliers
Giorgio
G
Bertoni
Francesco
F
Neri
Antonino
A
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
C495607:MAF protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051257:Proto-Oncogene Proteins c-maf