title: Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer.
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.
authors.affiliation: Oncogenesis and Molecular Virology Unit, Institut Pasteur, Paris Cedex 15, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cairo
authors.forename: Carolina
authors.initials: C
authors.lastname: Armengol
authors.forename: Aurélien
authors.initials: A
authors.lastname: De Reyniès
authors.forename: Yu
authors.initials: Y
authors.lastname: Wei
authors.forename: Emilie
authors.initials: E
authors.lastname: Thomas
authors.forename: Claire-Angélique
authors.initials: CA
authors.lastname: Renard
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
authors.forename: Asha
authors.initials: A
authors.lastname: Balakrishnan
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.forename: Lionel
authors.initials: L
authors.lastname: Gresh
authors.forename: Marco
authors.initials: M
authors.lastname: Pontoglio
authors.forename: Hélène
authors.initials: H
authors.lastname: Strick-Marchand
authors.forename: Florence
authors.initials: F
authors.lastname: Levillayer
authors.forename: Yann
authors.initials: Y
authors.lastname: Nouet
authors.forename: David
authors.initials: D
authors.lastname: Rickman
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gauthier
authors.forename: Sophie
authors.initials: S
authors.lastname: Branchereau
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Véronique
authors.initials: V
authors.lastname: Laithier
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Françoise
authors.initials: F
authors.lastname: Boman
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Michiels
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Francine
authors.initials: F
authors.lastname: Arbez-Gindre
authors.forename: Hélène
authors.initials: H
authors.lastname: Jouan
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rousselet-Chapeau
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.forename: Luc
authors.initials: L
authors.lastname: Marcellin
authors.forename: François
authors.initials: F
authors.lastname: Plenat
authors.forename: Dominique
authors.initials: D
authors.lastname: Zachar
authors.forename: Madeleine
authors.initials: M
authors.lastname: Joubert
authors.forename: Janick
authors.initials: J
authors.lastname: Selves
authors.forename: Dominique
authors.initials: D
authors.lastname: Pasquier
authors.forename: Paulette
authors.initials: P
authors.lastname: Bioulac-Sage
authors.forename: Michael
authors.initials: M
authors.lastname: Grotzer
authors.forename: Margaret
authors.initials: M
authors.lastname: Childs
authors.forename: Monique
authors.initials: M
authors.lastname: Fabre
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Buendia
mesh_terms: D000818:Animals; D002648:Child; D004252:DNA Mutational Analysis; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D051153:Wnt Proteins; D051176:beta Catenin