STANDARD_NAME	KOINUMA_COLON_CANCER_MSI_UP
SYSTEMATIC_NAME	M1096
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KOINUMA_COLON_CANCER_MSI_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in colorectal carcinoma samples positive for MSI (microsatellite instability) compared to the MSI negative ones.
DESCRIPTION_FULL	Mutation or epigenetic silencing of mismatch repair genes, such as MLH1 and MSH2, results in microsatellite instability (MSI) in the genome of a subset of colorectal carcinomas (CRCs). However, little is yet known of genes that directly contribute to tumor formation in such cancers. To characterize MSI-dependent changes in gene expression, we have now compared transcriptomes between fresh CRC specimens positive or negative for MSI (n=10 for each) with the use of high-density oligonucleotide microarrays harboring >44,000 probe sets. Correspondence analysis of the expression patterns of isolated MSI-associated genes revealed that the transcriptome of MSI+ CRCs is clearly distinct from that of MSI- CRCs. Such MSI-associated genes included that for AXIN2, an important component of the WNT signaling pathway. AXIN2 was silenced, apparently as a result of extensive methylation of its promoter region, specifically in MSI+ CRC specimens. Forced expression of AXIN2, either by treatment with 5'-azacytidine or by transfection with AXIN2 cDNA, resulted in rapid cell death in an MSI+ CRC cell line. These data indicate that epigenetic silencing of AXIN2 is specifically associated with carcinogenesis in MSI+ CRCs.
PMID	16247484
GEOID	GSE2138
AUTHORS	Koinuma K,Yamashita Y,Liu W,Hatanaka H,Kurashina K,Wada T,Takada S,Kaneda R,Choi YL,Fujiwara SI,Miyakura Y,Nagai H,Mano H
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200043_at,201533_at,202589_at,203476_at,203915_at,203932_at,204533_at,206858_s_at,208799_at,217933_s_at,218662_s_at,221505_at,225541_at,226545_at,227641_at,35201_at
GENE_SYMBOLS	ERH,CTNNB1,TYMS,TPBG,CXCL9,HLA-DMB,CXCL10,HOXC6,PSMB5,LAP3,NCAPG,ANP32E,RPL22L1,CD109,FBXL16,HNRNPL
FOUNDER_NAMES