STANDARD_NAME ZHAN_MULTIPLE_MYELOMA_CD2_DN SYSTEMATIC_NAME M17523 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ZHAN_MULTIPLE_MYELOMA_CD2_DN NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Top 50 down-regulated genes in cluster CD-2 of multiple myeloma samples with the charachteristic expression spike of CCND3 [GeneID=896]. DESCRIPTION_FULL To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF- and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature. PMID 16728703 GEOID GSE2658 AUTHORS Zhan F,Huang Y,Colla S,Stewart JP,Hanamura I,Gupta S,Epstein J,Yaccoby S,Sawyer J,Burington B,Anaissie E,Hollmig K,Pineda-Roman M,Tricot G,van Rhee F,Walker R,Zangari M,Crowley J,Barlogie B,Shaughnessy JD Jr CONTRIBUTOR Kevin Vogelsang CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3S: Subgroup = CD-2 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1556194_a_at,1558508_a_at,200650_s_at,201563_at,201590_x_at,202345_s_at,202934_at,204153_s_at,204175_at,205544_s_at,205943_at,206074_s_at,206653_at,208864_s_at,209302_at,209398_at,209581_at,209627_s_at,209631_s_at,209825_s_at,212218_s_at,212563_at,212771_at,213012_at,217755_at,217809_at,217848_s_at,218398_at,218587_s_at,219236_at,219366_at,219648_at,221297_at,221524_s_at,223278_at,224441_s_at,224975_at,225782_at,225968_at,226225_at,226733_at,227013_at,227599_at,227677_at,230766_at,235117_at,238718_at,240118_at,242181_at,243492_at GENE_SYMBOLS HSPA4L,C1orf53,LDHA,SORD,ANXA2,FABP5,HK2,MFNG,ZNF593,CR2,TDO2,HMGA1,POLR3G,TXN,POLR2H,H1-2,PLAAT3,OSBPL3,GPR37,UCK2,FASN,BOP1,FAM171A1,NEDD4,JPT1,BZW2,PPA1,MRPS30,POGLUT1,PAQR6,AVEN,MREG,GPRC5D,RRAGD,GJB2,USP45,NFIA,MSRB3,PRICKLE2,MCC,PFKFB2,LATS2,MB21D2,JAK3,GART,CHAC2,,,,THEM4 FOUNDER_NAMES