Full description or abstract |
Hepatoblastoma, the most common pediatric liver cancer, is tightly linked to excessive Wnt/beta-catenin signaling. Here, we used microarray analysis to identify two tumor subclasses resembling distinct phases of liver development and a discriminating 16-gene signature. beta-catenin activated different transcriptional programs in the two tumor types, with distinctive expression of hepatic stem/progenitor markers in immature tumors. This highly proliferating subclass was typified by gains of chromosomes 8q and 2p and upregulated Myc signaling. Myc-induced hepatoblastoma-like tumors in mice strikingly resembled the human immature subtype, and Myc downregulation in hepatoblastoma cells impaired tumorigenesis in vivo. Remarkably, the 16-gene signature discriminated invasive and metastatic hepatoblastomas and predicted prognosis with high accuracy. |
Source publication |
Pubmed 19061838 Authors: Cairo S,Armengol C,De Reyniès A,Wei Y,Thomas E,Renard CA,Goga A,Balakrishnan A,Semeraro M,Gresh L,Pontoglio M,Strick-Marchand H,Levillayer F,Nouet Y,Rickman D,Gauthier F,Branchereau S,Brugières L,Laithier V,Bouvier R,Boman F,Basso G,Michiels JF,Hofman P,Arbez-Gindre F,Jouan H,Rousselet-Chapeau MC,Berrebi D,Marcellin L,Plenat F,Zachar D,Joubert M,Selves J,Pasquier D,Bioulac-Sage P,Grotzer M,Childs M,Fabre M,Buendia MA |