STANDARD_NAME	BOYAULT_LIVER_CANCER_SUBCLASS_G56_UP
SYSTEMATIC_NAME	M1925
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BOYAULT_LIVER_CANCER_SUBCLASS_G56_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Up-regulated genes in hepatocellular carcinoma (HCC) subclass G56, defined by unsupervised clustering.
DESCRIPTION_FULL	Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ in risk factors and genetic alterations. We further investigated transcriptome-genotype-phenotype correlations in HCC. Global transcriptome analyses were performed on 57 HCCs and 3 hepatocellular adenomas and validated by quantitative RT-PCR using 63 additional HCCs. We determined loss of heterozygosity, gene mutations, promoter methylation of CDH1 and CDKN2A, and HBV DNA copy number for each tumor. Unsupervised transcriptome analysis identified 6 robust subgroups of HCC (G1-G6) associated with clinical and genetic characteristics. G1 tumors were associated with low copy number of HBV and overexpression of genes expressed in fetal liver and controlled by parental imprinting. G2 included HCCs infected with a high copy number of HBV and mutations in PIK3CA and TP53. In these first groups, we detected specific activation of the AKT pathway. G3 tumors were typified by mutation of TP53 and overexpression of genes controlling the cell cycle. G4 was a heterogeneous subgroup of tumors including TCF1-mutated hepatocellular adenomas and carcinomas. G5 and G6 were strongly related to beta-catenin mutations that lead to Wnt pathway activation; in particular, G6 tumors were characterized by satellite nodules, higher activation of the Wnt pathway, and E-cadherin underexpression. CONCLUSION: These results have furthered our understanding of the genetic diversity of human HCC and have provided specific identifiers for classifying tumors. In addition, our classification has potential therapeutic implications because 50% of the tumors were related to WNT or AKT pathway activation, which potentially could be targeted by specific inhibiting therapies.
PMID	17187432
GEOID	
AUTHORS	Boyault S,Rickman DS,de Reyniès A,Balabaud C,Rebouissou S,Jeannot E,Hérault A,Saric J,Belghiti J,Franco D,Bioulac-Sage P,Laurent-Puig P,Zucman-Rossi J
CONTRIBUTOR	Yujin Hoshida
CONTRIBUTOR_ORG	Broad Institute
EXACT_SOURCE	Table 4S: G56_UP
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200648_s_at,200795_at,203716_s_at,203717_at,203726_s_at,205815_at,208955_at,209806_at,209932_s_at,211478_s_at,212921_at,212922_s_at,213012_at,215001_s_at,217202_s_at,218610_s_at,219682_s_at,220510_at
GENE_SYMBOLS	GLUL,SPARCL1,DPP4,DPP4,LAMA3,REG3A,DUT,H2BC12,DUT,DPP4,,SMYD2,NEDD4,GLUL,GLUL,CPPED1,TBX3,RHBG
FOUNDER_NAMES