HEPATOBLASTOMA AND APC GENE MUTATION IN FAMILIAL ADENOMATOUS POLYPOSIS

Background-Hepatoblastoma is a rare, rapidly progressive, usually fata l childhood malignancy, which if confined to the liver can be cured by radical surgical resection. An association between hepatoblastoma and familial adenomatous polyposis (FAP), which is due to germline mutati on of the APC (adenomatous polyposis coli) gene, has been confirmed, b ut correlation with site of APC mutation has not been studied. Aim-To analyse the APC mutational spectrum in FAP families with hepatoblastom a as a possible basis to select kindreds for surveillance. Patients-Ei ght patients with hepatoblastoma in seven FAP kindreds were compared w ith 97 families with identified APC gene mutation in a large Registry. Methods-APC gene mutation was evaluated by RNase protection assay or in vitro synthesis protein assay. The chi(2) test and correlation were used for data analysis. Results-APC gene mutation was identified in a ll seven FAP kindreds in which an at risk member developed hepatoblast oma. A male predominance was noted (six of eight), similar to literatu re cases (18 of 25, p<0 . 01. Mutations were restricted to codons 141 to 1230, but no significant difference in site of mutation between ped igrees with and without hepatoblastoma was identified. Conclusions-Hep atoblastoma occurs primarily in boys in FAP kindreds and is associated with germline APC mutation in the 5' end of the gene. However, the si te of APC mutation cannot be used to predict occurrence of this extrac olonic cancer in FAP pedigrees.