STANDARD_NAME ROPERO_HDAC2_TARGETS SYSTEMATIC_NAME M8759 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ROPERO_HDAC2_TARGETS NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes up-regulated genes in cell lines with HDAC2 [GeneID=3066] loss of function (LOS). DESCRIPTION_FULL Although disruption of histone modification patterns is a common hallmark of human cancer, our knowledge of the mechanistic role of histone-modifying enzymes in its generation is very limited. We have recently identified an inactivating mutation in the histone deacetylase-2 (HDAC2) in sporadic carcinomas with microsatellite instability and in tumors arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. Since HDAC2 seems to be a central player in epigenetic gene repression, we wondered whether HDAC2-truncating mutations conferred a particular expression signature on these cancer cells. Using unsupervised clustering analysis in microsatellite-unstable colorectal cancer cell lines, we have found that HDAC2 mutant cells (RKO and Co115) show a characteristically different expression microarray signature from HDAC2 wild-type cells (HCT-116, SW48, HCT-15 and LoVo). HDAC2 mutant cells exhibit upregulation of tumor-promoting genes, such as those of tyrosine kinases, mediators of cell cycle progression and angiogenic factors. The overexpression of these genes is associated with a loss of HDAC2 recruitment and a gain of histone H4 hyperacetylation in their particular 5'-end promoters, as observed by chromatin immunoprecipitation. Transfection of wild-type HDAC2 in mutant cells reverted this epigenetic pattern by repressing the transforming genes in association with HDAC2 promoter occupancy. These results suggest a role for HDAC2 mutations in human tumorigenesis through the derepression of key genes from multiple cellular transformation pathways. PMID 18264134 GEOID AUTHORS Ropero S,Ballestar E,Alaminos M,Arango D,Schwartz S Jr,Esteller M CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACHE,ADD3,AP1S2,APLP1,APOA2,APOL2,AQP4,B4GALT6,BAHCC1,BIRC7,BNIP3L,C11orf68,C11orf9,C2orf3,CCDC85B,CDC42BPA,CEP57,CHIC2,CKMT2,COMP,CORO1C,CORO2B,CYP2D6,DDEF1,DGCR6L,DLEC1,DOPEY1,DPY19L1P1,EEF1D,EIF4EBP1,EMP3,EPHA2,FANCE,FCAR,FGF14,FIBP,FLJ14803,FUT5,GIP,GNLY,GP2,GSS,GZMB,HAPLN1,IGFBP7,INS,KCNJ6,KCNK3,KIAA0415,KIAA1509,KLK13,LOC157562,LOC399818,LOC440992,LOC646756,LOC93432,MACF1,MAG,MDM2,MGC87042,MMP16,MOG,MORN1,NADK,NCOA4,NEK3,NPY2R,OR1F2,PART1,PBX2,PCDHGA9,PCNXL2,PDE4D,PDX-1,PLA2G5,PPOX,PPP2R1B,PPP2R4,PTHLH,RABEPK,RAD52,RBM9,RBPMS,RUNX1,SAC,SEL1L,SEPT6,SERGEF,SHARPIN,SLC22A6,SLC6A2,SLFN12,SMAD6,SNAPC1,SPTBN2,ST3GAL1,STCH,STMN2,TADA2L,TBX2,TCL6,TLR6,TM6SF1,TNFAIP2,TNXB,TRGC2,TSTA3,TXNIP,TXNRD2,UBQLN3,UCHL3,WNT6,ZCCHC4,ZNF447 GENE_SYMBOLS ACHE,ADD3,AP1S2,APLP1,APOA2,APOL2,AQP4,B4GALT6,BAHCC1,BIRC7,BNIP3L,C11orf68,MYRF,GCFC2,CCDC85B,CDC42BPA,CEP57,CHIC2,CKMT2,COMP,CORO1C,CORO2B,CYP2D6,ASAP1,DGCR6L,DLEC1,DOP1A,DPY19L1P1,EEF1D,EIF4EBP1,EMP3,EPHA2,FANCE,FCAR,FGF14,FIBP,TMEM209,FUT5,GIP,GNLY,GP2,GSS,GZMB,HAPLN1,IGFBP7,INS,KCNJ6,KCNK3,AP5Z1,CCDC88C,KLK13,,EEF1AKMT2,RPS20P14,,MGAM2,MACF1,MAG,MDM2,STEAP1B,MMP16,MOG,MORN1,NADK,NCOA4,NEK3,NPY2R,OR1F2P,PART1,PBX2,PCDHGA9,PCNX2,PDE4D,PDX1,PLA2G5,PPOX,PPP2R1B,PTPA,PTHLH,RABEPK,RAD52,RBFOX2,RBPMS,RUNX1,ADCY10,SEL1L,SEPTIN6,SERGEF,SHARPIN,SLC22A6,SLC6A2,SLFN12,SMAD6,SNAPC1,SPTBN2,ST3GAL1,HSPA13,STMN2,TADA2A,TBX2,TCL6,TLR6,TM6SF1,TNFAIP2,TNXB,TRGC2,GFUS,TXNIP,TXNRD2,UBQLN3,UCHL3,WNT6,ZCCHC4,ZSCAN18 FOUNDER_NAMES