Gene expression profiling in hepatoblastomas

Hepatoblastomas represent the most frequent malignant liver tumors in children. Although crucial signalling pathways involved in their pathogenesis such as the IGF-II and WNT pathways have been identified, a systematic search for overexpressed mRNA species has not been performed yet. In this study we have established mRNA expression profiles using oligonucleotide arrays (Affymetrix) of 3 hepatoblastomas without preoperative treatment with chemotherapy, corresponding adjacent liver tissue samples and two fetal liver samples. Bioinformatic analysis has uncovered several genes highly overexpressed in hepatoblastomas as compared to normal pediatric and fetal liver. These included alpha-fetoprotein which is already used as a diagnostic marker but also novel genes such as the Dickkopf-1 (Dkk-1) gene. Dkk-1 encodes a soluble antagonist of the WNT signalling pathway and has been previously identified to be overexpressed in hepatoblastomas by subtractive suppression hybridization (Wirths et al., Lab Invest. 2003; 83: 429–34). Genes highly overexpressed in hepatoblastomas may serve as novel diagnostic or therapeutic targets in this malignant disease.