Nuclear localization and mutation of beta-catenin in medulloblastomas

J Neuropathol Exp Neurol. 2000 Apr;59(4):333-7. doi: 10.1093/jnen/59.4.333.


The adenomatous polyposis coli (APC) gene, a member of the Wingless/Wnt signal transduction pathway, has been implicated in the development of medulloblastomas in Turcot's syndrome. beta-catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or beta-catenin can stabilize beta-catenin protein. Stabilized beta-catenin complexes with Tcf/Lef transcription factors and moves from the cytoplasm into the nucleus where it regulates the transcription of c-Myc and other genes. Nuclear localization of beta-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of beta-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear beta-catenin staining was present in 9 of the sporadic tumors (18%) and in the 1 medulloblastoma from a Turcot's patient. The remaining 41 cases did not show nuclear staining. This confirms earlier observations that Wingless/Wnt signaling is involved in a subset of sporadic medulloblastomas. We also examined 48 glial and meningeal CNS tumors, all of which were negative for nuclear beta-catenin. Exon 3 of beta-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear beta-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved beta-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for beta-catenin mutations in medulloblastomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Binding Sites / genetics
  • Cell Nucleus / metabolism*
  • Cell Nucleus / pathology
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA Mutational Analysis
  • Exons / genetics
  • Fetal Diseases / pathology
  • Fetal Diseases / physiopathology
  • Humans
  • Immunohistochemistry
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Middle Aged
  • Mutation
  • Phosphorylation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction / genetics
  • Survival Rate
  • Trans-Activators*
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin