STANDARD_NAME HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP SYSTEMATIC_NAME M14127 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated in multiple myeloma (MM) cell lines treated with both decitabine [PubChem=451668] TSA [PubChem=5562]. DESCRIPTION_FULL To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2'-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM. PMID 18172295 GEOID AUTHORS Heller G,Schmidt WM,Ziegler B,Holzer S,Müllauer L,Bilban M,Zielinski CC,Drach J,Zöchbauer-Müller S CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 211456_x_at,211781_x_at,213685_at,215594_at,222296_at,222315_at,AASS,ABAT,ABCB1,ABHD5,ABTB2,ACADSB,ACSL3,ADARB1,ADCY9,AGRN,AHR,AKAP12,AKAP13,AKR1C3,ALCAM,ALDH1A3,ALDH2,ALDH4A1,ALDOC,ALPP,ALPPL2,ANKRD6,APG12L,APLP1,APLP2,APOE,AREG,ARG2,ARL6IP,ARMCX2,ASMTL,ATF7IP2,ATP13A2,ATP1B1,ATP6AP2,ATP6V0D1,ATP6V1D,AZI1,BACH,BAIAP2,BAIAP3,BCL6,BEXL1,BG1,BIK,BIN1,BIRC3,BMP2K,BRCA2,BTG1,C10orf3,C14orf78,C19orf28,C19orf36,C1S,C20orf12,C20orf19,C2orf31,C3,C3F,C3orf14,CACNA1G,CALM1,CAMTA1,CCK,CCNA1,CCNF,CD24,CD9,CDC14B,CDH1,CDH19,CDKL3,CDKN1A,CDKN1C,CEL,CFH,CGA,CGB,CGREF1,CNTNAP2,COL14A1,COL6A2,COTL1,CRIP2,CRISPLD2,CSPG3,CSPG5,CSRP2,CSTA,CTH,CTSL2,CXCL11,CYLN2,CYP1A1,CYP1B1,CYP26B1,DAZL,DBN1,DDAH2,DDX4,DDX43,DHRS2,DHRS8,DLG7,DLX2,DMRT1,DNAH3,DNM3,DPEP3,DRE1,DUSP1,DUSP2,DYRK3,DZIP1,DZIP3,ECAT8,EFHC1,EFNB2,EGR1,EGR2,EGR4,EHHADH,EIF4EBP2,ENAH,ENPP2,EPAS1,EPHA3,ERO1LB,FAM49A,FBN1,FBP2,FDXR,FER,FER1L3,FGD6,FGFR1,FGFR3,FGFR4,FHL1,FKBP1B,FLJ10178,FLJ10922,FLJ12584,FLJ14627,FLJ20130,FLJ20507,FLJ21159,FLJ22833,FLNA,FLNB,FN1,FOS,FOXG1B,FSCN1,FTCD,FTL,FUCA1,G1P3,G6PD,GAGE1,GAGE2,GAGE3,GAGE4,GAGE5,GAL,GATA3,GLCE,GLDC,GLUL,GLULD1,GM2A,GMPR,GNS,GPM6A,GPSM2,GRN,GSN,H1F0,H2AFB3,HABP4,HBA1,HBA2,HES1,HIST1H1C,HIST1H1T,HIST1H2AC,HIST1H2AE,HIST1H2AG,HIST1H2AI,HIST1H2AM,HIST1H2BB,HIST1H2BC,HIST1H2BG,HIST1H2BI,HIST1H3B,HIST1H3D,HIST1H3G,HIST1H3H,HIST1H3J,HIST1H4B,HIST1H4H,HIST1H4K,HIST2H2AA,HIST2H2BE,HIST2H4,HIST3H2A,HIST3H3,HK1,HLA-DPA1,HLA-DPB1,HLA-DQA1,HLA-DRB1,HLA-DRB4,HN1,HOXA1,HPGD,HPSE,HSD17B1,HSPA1A,HSPA2,HUMPPA,ID1,ID2,IER3,IFI27,IFIT1,IGFBP3,IL13RA1,IL15,ING1,ITGA6,ITGA7,ITGBL1,ITSN1,JAG1,JAG2,JARID1B,JUP,KATNB1,KCNN2,KCTD12,KHK,KIAA0404,KIAA0415,KIAA0446,KIAA0513,KIAA0913,KIAA1109,KIAA1117,KIF4A,KIF5C,KLF2,KRT18,L1CAM,LAMP3,LHX2,LIFR,LONP,LPPR2,MAFB,MAGEA11,MAGEA3,MAGEA4,MAGEA6,MAGEA9,MAGEB2,MAGEC1,MAPK8IP1,MAPRE3,MAPT,MARCKSL1,MEF2C,MET,MGC14376,MGST3,MICAL-L2,MICAL2,MLF1,MSH5,MSX1,MT1E,MT1H,MT1X,MT2A,MYBL1,MYCN,MYO9B,NAB2,NAP1L3,NAT1,NCAM1,NEDD9,NEFL,NEU1,NFYA,NGFRAP1,NPAL3,NPTX2,NR1H4,NR4A1,NR4A2,NRGN,NRXN1,NTS,NUDT11,NUP93,NXN,OAT,ODC1,ODZ1,OGDHL,ORC5L,PAEP,PCDH9,PCLO,PCTK3,PDGFRL,PDLIM5,PEG10,PFKFB3,PFN2,PGBD5,PGF,PHLDA2,PIGV,PIK3CD,PLEC1,PLK2,PLS1,PLXNB3,POLR2L,POR,PPARD,PPL,PPM1E,PPP2R3B,PRKAR2B,PRKCB1,PRPH,PRSS2,PSAP,PTD015,PTGER4,PTK2,PYY,RAB13,RAB6IP1,RAI2,RASGRP2,RBM9,RCN3,RHCE,RHOB,RIS1,RNF128,RNU2,RPIB9,RPS20,RPS6KA2,RRAD,RRAS,RRBP1,RTN2,S100A4,SART2,SAT,SCP2,SDC4,SEPP1,SEPT4,SERPINB5,SERPINE2,SERPINF1,SERPINI1,SFXN3,SGKL,SH3BGR,SH3GL3,SILV,SLC12A8,SLC16A3,SLC16A4,SLC17A7,SLC25A31,SLC4A8,SLC6A8,SLC9A1,SMARCD3,SMPD3,SNAI1,SNAP23,SNAP25,SORBS1,SORT1,SOX4,SPAG6,SPAG9,SPIB,SPINK2,SPP1,SPTLC2,SQSTM1,SSX1,SSX2,SSX3,STAT1,STAT3,SWAP70,SYN1,SYT1,SYT11,TAC1,TADA3L,TAOK3,TFAP2C,TFEC,TFPI,TFPI2,TFRC,TIMP1,TIMP3,TKTL1,TLE4,TLN2,TM4SF13,TMEM47,TMOD1,TMSL8,TNRC9,TOP2A,TPM1,TRIP6,TROAP,TSPAN12,TST,TTLL1,TUBA3,TUBB2,TUBB2B,TUBB3,TUBB4,TUBB6,TUBG1,TUFT1,TULP3,TXNIP,TXNRD3,UBD,UBE2S,ULBP2,UNC119,VCX,WASF1,WBP5,WDR7,WIG1,ZCCHC14,ZNF10,ZNF238,ZNF297B,ZNF556,ZNF557,ZYG11BL GENE_SYMBOLS MT1H,,ELOA-AS1,,,,AASS,ABAT,ABCB1,ABHD5,ABTB2,ACADSB,ACSL3,ADARB1,ADCY9,AGRN,AHR,AKAP12,AKAP13,AKR1C3,ALCAM,ALDH1A3,ALDH2,ALDH4A1,ALDOC,ALPP,ALPG,ANKRD6,ATG12,APLP1,APLP2,APOE,AREG,ARG2,ARL6IP1,ARMCX2,ASMTL,ATF7IP2,ATP13A2,ATP1B1,ATP6AP2,ATP6V0D1,ATP6V1D,CEP131,ACOT7,BAIAP2,BAIAP3,BCL6,BEX4,ACSBG1,BIK,BIN1,BIRC3,BMP2K,BRCA2,BTG1,CEP55,AHNAK2,MFSD12,IZUMO4,C1S,DZANK1,KIZ,FZD5,C3,LPCAT3,C3orf14,CACNA1G,CALM1,CAMTA1,CCK,CCNA1,CCNF,CD24,CD9,CDC14B,CDH1,CDH19,CDKL3,CDKN1A,CDKN1C,CEL,CFH,CGA,CGB3,CGREF1,CNTNAP2,COL14A1,COL6A2,COTL1,CRIP2,CRISPLD2,NCAN,CSPG5,CSRP2,CSTA,CTH,CTSV,CXCL11,CLIP2,CYP1A1,CYP1B1,CYP26B1,DAZL,DBN1,DDAH2,DDX4,DDX43,DHRS2,HSD17B11,DLGAP5,DLX2,DMRT1,DNAH3,DNM3,DPEP3,KLHL24,DUSP1,DUSP2,DYRK3,DZIP1,DZIP3,TDRD12,EFHC1,EFNB2,EGR1,EGR2,EGR4,EHHADH,EIF4EBP2,ENAH,ENPP2,EPAS1,EPHA3,ERO1B,CYRIA,FBN1,FBP2,FDXR,FER,MYOF,FGD6,FGFR1,FGFR3,FGFR4,FHL1,FKBP1B,RADX,TMEM143,ARMC9,RNFT2,NUP62CL,TMEM127,MAP9,NABP1,FLNA,FLNB,FN1,FOS,FOXG1,FSCN1,FTCD,FTL,FUCA1,IFI6,G6PD,GAGE1,GAGE2A,,,,GAL,GATA3,GLCE,GLDC,GLUL,LGSN,GM2A,GMPR,GNS,GPM6A,GPSM2,GRN,GSN,H1-0,H2AB3,HABP4,HBA1,HBA2,HES1,H1-2,H1-6,H2AC6,H2AC8,H2AC11,H2AC13,H2AC17,H2BC3,H2BC4,H2BC8,H2BC10,H3C2,H3C4,H3C8,H3C10,H3C12,H4C2,H4C8,H4C12,H2AC18,H2BC21,H4C14,H2AC25,H3-4,HK1,HLA-DPA1,HLA-DPB1,HLA-DQA1,HLA-DRB1,HLA-DRB4,JPT1,HOXA1,HPGD,HPSE,HSD17B1,HSPA1A,HSPA2,CDR2L,ID1,ID2,IER3,IFI27,IFIT1,IGFBP3,IL13RA1,IL15,ING1,ITGA6,ITGA7,ITGBL1,ITSN1,JAG1,JAG2,KDM5B,JUP,KATNB1,KCNN2,KCTD12,KHK,ATG2A,AP5Z1,SLC25A44,KIAA0513,ZSWIM8,BLTP1,DOP1A,KIF4A,KIF5C,KLF2,KRT18,L1CAM,LAMP3,LHX2,LIFR,LONP2,PLPPR2,MAFB,MAGEA11,MAGEA3,MAGEA4,MAGEA6,MAGEA9,MAGEB2,MAGEC1,MAPK8IP1,MAPRE3,MAPT,MARCKSL1,MEF2C,MET,MIR22HG,MGST3,MICALL2,MICAL2,MLF1,MSH5,MSX1,MT1E,MT1H,MT1X,MT2A,MYBL1,MYCN,MYO9B,NAB2,NAP1L3,NAT1,NCAM1,NEDD9,NEFL,NEU1,NFYA,BEX3,NIPAL3,NPTX2,NR1H4,NR4A1,NR4A2,NRGN,NRXN1,NTS,NUDT11,NUP93,NXN,OAT,ODC1,TENM1,OGDHL,ORC5,PAEP,PCDH9,PCLO,CDK18,PDGFRL,PDLIM5,PEG10,PFKFB3,PFN2,PGBD5,PGF,PHLDA2,PIGV,PIK3CD,PLEC,PLK2,PLS1,PLXNB3,POLR2L,POR,PPARD,PPL,PPM1E,PPP2R3B,PRKAR2B,PRKCB,PRPH,PRSS2,PSAP,AAMDC,PTGER4,PTK2,PYY,RAB13,DENND5A,RAI2,RASGRP2,RBFOX2,RCN3,RHCE,RHOB,UQCRFS1,RNF128,,RUNDC3B,RPS20,RPS6KA2,RRAD,RRAS,RRBP1,RTN2,S100A4,DSE,SAT1,SCP2,SDC4,SELENOP,SEPTIN4,SERPINB5,SERPINE2,SERPINF1,SERPINI1,SFXN3,SGK3,SH3BGR,SH3GL3,PMEL,SLC12A8,SLC16A3,SLC16A4,SLC17A7,SLC25A31,SLC4A8,SLC6A8,SLC9A1,SMARCD3,SMPD3,SNAI1,SNAP23,SNAP25,SORBS1,SORT1,SOX4,SPAG6,SPAG9,SPIB,SPINK2,SPP1,SPTLC2,SQSTM1,SSX1,SSX2,SSX3,STAT1,STAT3,SWAP70,SYN1,SYT1,SYT11,TAC1,TADA3,TAOK3,TFAP2C,TFEC,TFPI,TFPI2,TFRC,TIMP1,TIMP3,TKTL1,TLE4,TLN2,TSPAN13,TMEM47,TMOD1,TMSB15A,TOX3,TOP2A,TPM1,TRIP6,TROAP,TSPAN12,TST,TTLL1,TUBA1A,TUBB2A,TUBB2B,TUBB3,TUBB4A,TUBB6,TUBG1,TUFT1,TULP3,TXNIP,TXNRD3,UBD,UBE2S,ULBP2,UNC119,VCX,WASF1,TCEAL9,WDR7,ZMAT3,ZCCHC14,ZNF10,ZBTB18,ZBTB43,ZNF556,ZNF557,ZER1 FOUNDER_NAMES