Document Detail


Characterization of oncogene dysregulation in multiple myeloma by combined FISH and DNA microarray analyses.
MedLine Citation:
PMID:  15543617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sonia Fabris; Luca Agnelli; Michela Mattioli; Luca Baldini; Domenica Ronchetti; Fortunato Morabito; Donata Verdelli; Lucia Nobili; Daniela Intini; Vincenzo Callea; Caterina Stelitano; Luigia Lombardi; Antonino Neri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Genes, chromosomes & cancer     Volume:  42     ISSN:  1045-2257     ISO Abbreviation:  Genes Chromosomes Cancer     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2004-12-13     Completed Date:  2005-07-19     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  9007329     Medline TA:  Genes Chromosomes Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  117-27     Citation Subset:  IM    
Copyright Information:
(c) 2004 Wiley-Liss, Inc.
Affiliation:
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, UO Ematologia 1, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/CCND3 protein, human; 0/Carrier Proteins; 0/Cyclin D3; 0/Cyclins; 0/DNA-Binding Proteins; 0/MAFB protein, human; 0/Macrophage-Activating Factors; 0/MafB Transcription Factor; 0/Oncogene Proteins; 0/Oncogene Proteins, Fusion; 0/Receptors, Fibroblast Growth Factor; 0/Repressor Proteins; 0/Transcription Factors; 136601-57-5/Cyclin D1; EC 2.1.1.43/Histone-Lysine N-Methyltransferase; EC 2.1.1.43/WHSC1 protein, human; EC 2.7.10.1/FGFR3 protein, human; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3

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