Hepatoblastoma is a rare hepatic malignancy that occurs in children with an average age of 2 or 3 years and is known to be one of the extracolonic manifestations of familial adenomatous polyposis. Only a single hepatoblastoma with a germ-line mutation of the adenomatous polyposis coli (APC) gene has been reported thus far. To elucidate the possible roles of APC gene alterations in sporadic hepatoblastomas, we examined loss of heterozygosity (LOH) at the APC and MCC loci and performed a sequencing analysis of a part of the APC gene, including the mutation cluster region, in 13 hepatoblastomas of non-familial adenomatous polyposis patients. LOH at the APC and/or MCC loci was observed in four of seven (57%) informative cases. Of the 13 cases, somatic mutations were detected in 8 (61.5%), with 9 (69%) cases showing genetic alterations in the APC gene as LOH or somatic mutations. Two cases demonstrated double mutations. Furthermore, the nature of the somatic mutations observed in the present study was unusual because 9 of the 10 mutations were missense, with only 1 case featuring a frame-shift mutation due to an insertion. Previous reports have described almost all (>90%) mutations of the APC gene in colorectal tumors to result in a truncated APC protein due to either frame-shift or nonsense mutations. These findings suggest that a mutation of the APC gene may play an important role in the genesis of sporadic hepatoblastomas, and the mechanisms of APC gene alteration may be different from those reported previously for colorectal tumors.


Supported by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture and the Smoking Research Foundation.

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