Hepatic stem-like phenotype and interplay of Wnt/beta-catenin and Myc signaling in aggressive childhood liver cancer

Cancer Cell. 2008 Dec 9;14(6):471-84. doi: 10.1016/j.ccr.2008.11.002.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Child
  • DNA Mutational Analysis
  • Humans
  • Liver / metabolism*
  • Liver Neoplasms / metabolism*
  • Mice
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Reproducibility of Results
  • Signal Transduction
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • Proto-Oncogene Proteins c-myc
  • Wnt Proteins
  • beta Catenin