High frequency of beta-catenin mutations in hepatoblastoma

Pediatr Surg Int. 2001 Sep;17(7):508-12. doi: 10.1007/s003830000576.


Hepatoblastoma (HB) is an embryonic neoplasm representing the most frequent malignant liver tumour in childhood. Its tumourigenesis at the molecular level is still poorly understood, and candidate genes are yet to be identified. According to recent reports describing beta-catenin mutations (BCM) at hot-spot regions involving exon 3 in several types of malignancies including HB, we investigated BCM in 16 HBs classified into different histological types. One tumour had been previously confirmed to harbour adenomatous polyposis coli (APC) mutations that exhibit a similar oncogenic effect to that of BCM. Mutations in both exon 3 and its flanking region of the beta-catenin gene were investigated and determined. Twelve tumours (75%) revealed pathogenic BCM, including 5 with missense mutations at codons 32, 34, or 37 and 7 with interstitial deletions that partially or totally affected exon 3. All 7 deletions were in-frame deletions without frameshift. A single nucleotide change at codon 31 regarded as non-pathogenic polymorphism was detected in the tumour possessing APC mutations. Therefore, a total of 13 tumours (81%) were compromised by an enhanced beta-catenin-mediated transcription pathway. Mutations were observed in every histological type of HB. The very high frequency without correlation to histological type indicates that BCM are crucial events in the tumourigenesis of HB.

MeSH terms

  • Child
  • Child, Preschool
  • Chromosome Deletion
  • Cytoskeletal Proteins / genetics*
  • Female
  • Hepatoblastoma / genetics*
  • Humans
  • Infant
  • Liver Neoplasms / genetics*
  • Male
  • Mutation, Missense
  • Trans-Activators*
  • Transcription, Genetic
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin