beta-catenin accumulation and mutation of the CTNNBI gene in hepatoblastoma

Hepatoblastoma is a rare malignant tumor of the liver that occurs in childr en at an average age of 2 to 3 years. Epidemiologic studies have shown an i ncreased frequency of this tumor type in families affected by adenomatous p olyposis coli. In addition to the epidemiologic data, molecular genetic stu dies suggest that inactivation of the APC tumor suppressor may be involved in hepatoblastoma tumorigenesis, A major function of APC is the downregulat ion of beta-catenin, a transcription-activating protein with oncogenic pote ntial. In an ongoing immunohistochemical study of beta-catenin expression i n sporadic cases of tumor types that are associated with adenomatous polypo sis coli, we observed increased beta-catenin levels in the cytoplasm and in the nuclei of three investigated hepatoblastomas. Sequencing of exon 3 of the beta-catenin gene (CTNNB1) revealed an activating mutation in one of th e tumor samples. Our data indicate for the first time that beta-catenin acc umulation may play a role in the development of hepatoblastoma and that act ivating mutations of the beta-catenin gene may substitute biallelic APC ina ctivation in this tumor type. Genes Chromosomes Cancer 25:399-402, 1999. (C ) 1999 Wiley-Liss, Inc.