03074nas a2200325   4500008004100000245011200041210006900153300001100222490000700233520182100240653001102061653002302072653009602095653012202191653006602313653004102379653002302420100001402443700001602457700001302473700001402486700002602500700002402526700001902550700001502569700001602584700002102600700002102621856010602642       2006                        eng d00aIdentification of overexpressed genes in frequently gained/amplified chromosome regions in multiple myeloma0 aIdentification of overexpressed genes in frequently gainedamplif  a184-910 v913 aBACKGROUND AND OBJECTIVES: Multiple myeloma (MM) is a malignancy characterized by clonal expansion of plasma cells. In 50% of the cases, the neoplastic transformation begins with a chromosomal translocation that juxtaposes the IGH gene locus to an oncogene. Gene copy number changes are also frequent in MM but less characterized than in other neoplasias. We aimed to characterize genes that are amplified and overexpressed in human myeloma cell lines (HMCL) to provide putative molecular targets for MM therapy. DESIGN AND METHODS: Nine HMCL were characterized by fluorescent in situ hybridization, comparative genomic hybridization (CGH) and cDNA microarrays for gene expression profiling and copy number changes. RESULTS: After defining the IGH-translocations present in the cell lines, we conducted expression-profiling analysis. Supervised analysis identified 166 genes with significantly different expression among the cell lines harboring MMSET/FGFR3 (4p16), MAF (16q) and CCND1 (11q13) rearrangements. Array-CGH was then performed. Five chromosomes recurrently affected by gains/amplifications in primary samples and cell lines were analyzed in detail. Sixty amplified and overexpressed genes were found and 25 (42%) of them were only overexpressed when amplified; moreover, six showed a significant association between overexpression and gain/amplification. We also found co-amplification and overexpression for genes located within the same amplicons, such as MALT1 and BCL2. INTERPRETATION AND CONCLUSIONS: Parallel analysis of gene copy numbers and expression levels by cDNA microarray in MM allowed efficient identification of genes whose expression levels are elevated because of increased copy number. This is the first time that MALT1 and BCL2 have been shown to be overexpressed and amplified in MM.10aB-Cell10aCaspases Cell Line10aHuman *Gene Amplification Gene Dosage Gene Expression Profiling *Gene Expression Regulation10aMarginal Zone/genetics Multiple Myeloma/*genetics Neoplasm Proteins/genetics Proto-Oncogene Proteins c-bcl-2/genetics10aNeoplasm Humans Immunoglobulin Heavy Chains/genetics Lymphoma10aNeoplastic Gene Rearrangement *Genes10aTumor *Chromosomes1 aLargo, C.1 aAlvarez, S.1 aSaez, B.1 aBlesa, D.1 aMartin-Subero, J., I.1 aGonzalez-Garcia, I.1 aBrieva, J., A.1 aDopazo, J.1 aSiebert, R.1 aCalasanz, M., J.1 aCigudosa, J., C.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16461302