STANDARD_NAME MUNSHI_MULTIPLE_MYELOMA_UP SYSTEMATIC_NAME M4517 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MUNSHI_MULTIPLE_MYELOMA_UP NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Genes up-regulated in multiple myeloma (MM) compared to normal plasma cells from the patient's identical twin. DESCRIPTION_FULL Genetic heterogeneity between individuals confounds the comparison of gene profiling of multiple myeloma (MM) cells versus normal plasma cells (PCs). To overcome this barrier, we compared the gene expression profile of CD138+ MM cells from a patient bone marrow (BM) sample with CD138+ PCs from a genetically identical twin BM sample using microarray profiling. Two hundred and ninety-six genes were up-regulated and 103 genes were down-regulated at least 2-fold in MM cells versus normal twin PCs. Highly expressed genes in MM cells included cell survival pathway genes such as mcl-1, dad-1, caspase 8, and FADD-like apoptosis regulator (FLIP); oncogenes/transcriptional factors such as Jun-D, Xbp-1, calmodulin, Calnexin, and FGFR-3; stress response and ubiquitin/proteasome pathway-related genes and various ribosomal genes reflecting increased metabolic and translational activity. Genes that were down-regulated in MM cells versus healthy twin PCs included RAD51, killer cell immunoglobulin-like receptor protein, and apoptotic protease activating factor. Microarray results were further confirmed by Western blot analyses, immunohistochemistry, fluorescent in situ hybridization (FISH), and functional assays of telomerase activity and bone marrow angiogenesis. This molecular profiling provides potential insights into mechanisms of malignant transformation in MM. For example, FGFR3, xbp-1, and both mcl-1 and dad-1 may mediate transformation, differentiation, and survival, respectively, and may have clinical implications. By identifying genes uniquely altered in MM cells compared with normal PCs in an identical genotypic background, the current study provides the framework to identify novel therapeutic targets. PMID 12969976 GEOID AUTHORS Munshi NC,Hideshima T,Carrasco D,Shammas M,Auclair D,Davies F,Mitsiades N,Mitsiades C,Kim RS,Li C,Rajkumar SV,Fonseca R,Bergsagel L,Chauhan D,Anderson KC CONTRIBUTOR Kevin Vogelsang CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AA158243,AA932443,AB002405,AB002533,AB012851,AB018549,AB028986,AF005775,AF015950,AF040704,AF052432,AF054183,AF054187,AF068864,AI557240,AI827730,AI912041,AJ005259,AL031133,AL031228,AW003733,D00017,D00760,D00761,D13628,D15057,D45248,D89667,J04111,J04164,J04617,L06797,L08246,L10284,L11672,L34657,M13207,M19311,M19481,M26880,M30938,M37435,M60556,M60614,M64347,M69043,M76125,M83221,M84739,M96233,S57235,S76992,S81003,T58471,U03858,U18543,U34995,U58198,U68566,U73824,U77735,U83659,U88964,V01512,W72186,X04803,X13794,X15187,X16663,X56681,X61615,X62654,X74929,X87949,X97671,X98296,X98743,Y07661,Z22533,Z29574,Z69043,Z93930 GENE_SYMBOLS FKBP2,FZR1,TMC6,KPNA4,MSI1,LY96,USP22,CFLAR,TERT,CYB561D2,KATNB1,RAN,NACA,PAK3,DBI,CNNM2,HSPE1,,ZC3H12D,COL11A2,RHOD,ANXA2,PSMA2,PSMB1,ANGPT1,DAD1,PSME2,,JUN,IFITM1,EEF1A1,CXCR4,MCL1,CANX,ZNF91,,CSF2,CALM2,,UBC,XRCC5,CSF1,TGFB3,WT1-AS,FGFR3,NFKBIA,AXL,RELB,CALR,GSTM4,CD68,VAV2,UBE2L3,UQCR11,FLT3LG,TRIM32,,FOXK2,HAX1,EIF4G2,PIM2,ABCC3,ISG20,FOS,S100A4,UBB,LDHB,HSP90B1,HCLS1,JUND,LIFR,CD63,KRT8,HSPA5,EPOR,USP9X,DDX18,USF2,ACVRL1,TNFRSF17,SSR4,XBP1 FOUNDER_NAMES