Thus, our present results suggested that the gain of function mutation of beta-catenin played a crucial role in the malignant progression of HBL in vivo.
Immunohistochemical analysis of beta-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear beta-catenin immunostaining in undifferentiated cells.
Comparison to previously published data on this series of HB revealed that the number of chromosomal imbalances was significantly higher in HB tumors with loss of heterozygosity on 11p (P = 0.03), whereas in five of 10 HB biopsies without chromosomal imbalances, beta-catenin gene mutations were found.
Our data indicate for the first time that beta-catenin accumulation may play a role in the development of hepatoblastoma and that activating mutations of the beta-catenin gene may substitute biallelic APC inactivation in this tumor type.
Using single-strand conformational polymorphism analysis, deletion screening by PCR, and direct sequencing, we found a high frequency of beta-catenin mutations in sporadic HBs (48%).