Somatic mutations of beta-catenin play a crucial role in the tumorigenesis of sporadic hepatoblastoma.
Hepatoblastoma (HB) is the most common malignant hepatic tumor during early childhood. Its molecular pathogenesis is still poorly understood. Mutations of adenomatous polyposis coli (APC) gene have been identified in sporadic cases and in individuals associated with familial adenomatous polyposis syndrome. beta-catenin is a key element in the cadherin-mediated cell adhesion system and Wnt/wingless pathway, and is controlled by APC. APC affects the degradation of beta-catenin by its NH(2)-terminal phosphorylation on the serine/threonine residues of exon 3. Mutations of these phosphorylation sites are primary targets for activating mutations in several types of human cancer and lead to nuclear accumulation of beta-catenin protein. In this study, we examined nine patients with HB using immunohistochemistry and direct DNA sequencing. All nine cases showed predominant nuclear expression of beta-catenin. Eight cases (89%) showed mutations involving exon 3 of the beta-catenin gene, including five with deletions and three with missense mutations. All five deletions were in-frame deletions without frameshift. The very high frequency of mutations in the beta-catenin gene suggests that beta-catenin mutations are crucial in the tumorigenesis of HB.
Jeng
Y M
YM
Department of Pathology, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan.
Wu
M Z
MZ
Mao
T L
TL
Chang
M H
MH
Hsu
H C
HC
D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018197:Hepatoblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin