Beckwith-Wiedemann syndrome-associated hepatoblastoma: wnt signal activation occurs later in tumorigenesis in patients with 11p15.5 uniparental disomy

Pediatr Dev Pathol. 2003 Jul-Aug;6(4):299-306. doi: 10.1007/s10024-003-1009-1.


Beckwith-Wiedemann syndrome (BWS) patients with chromosome 11p15.5 uniparental isodisomy (UPD) have an increased risk for developing embryonal tumors. UPD in these patients involves maternal loss of heterozygosity (LOH) and paternal duplication, which leads to tissue overgrowth and tumor development. Although 11p15.5 UPD predisposes to tumorigenesis, the events leading to tumorigenesis in UPD patients remains unknown. We have examined two hepatoblastomas in the BWS patients with UPD to determine the sequence of genetic events. Constitutional 11p15.5 LOH was detected in the blood or nonneoplastic liver of the BWS patients with hepatoblastoma. Mutation of beta-catenin gene (CTNNB1) was found in one hepatoblastoma. Although mutations in CTNNB1 were not found in the second hepatoblastoma, nuclear accumulation of beta-catenin was detected. However, mutation of CTNNB1 or nuclear accumulation of beta-catenin was not detected in the tissue with hepatomegaly which contains UPD cells. These data indicate that Wnt signal activation can be involved as a later event in BWS-associated hepatoblastoma involving 11p15.5 UPD.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Substitution
  • Beckwith-Wiedemann Syndrome / complications*
  • Beckwith-Wiedemann Syndrome / genetics*
  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, Pair 11*
  • DNA Methylation
  • DNA Mutational Analysis
  • Female
  • Hepatoblastoma / etiology*
  • Hepatoblastoma / metabolism
  • Hepatoblastoma / pathology
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Loss of Heterozygosity
  • Mutation
  • Proline
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • Repressor Proteins / genetics
  • Serine
  • Signal Transduction
  • Uniparental Disomy / genetics*
  • Wnt Proteins
  • Zebrafish Proteins*


  • Adaptor Proteins, Signal Transducing
  • CTNNBIP1 protein, human
  • Cell Cycle Proteins
  • H19 long non-coding RNA
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Repressor Proteins
  • Wnt Proteins
  • Zebrafish Proteins
  • Serine
  • Proline