Nuclear localization and mutation of β-catenin in medulloblastomas

Charles G Eberhart, Tarik Tihan, Peter C. Burger

Research output: Contribution to journalArticle

Abstract

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. β-Catenin also functions in this highly conserved signaling pathway and is instrumental in growth and development. Mutations in either APC or β-catenin can stabilize β-catenin protein. Stabilized β-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 β-catenin therefore implies activation of the signaling pathway. We have analyzed the subcellular localization of β-catenin in 51 sporadic medulloblastomas and in 1 medulloblastoma arising in a patient with Turcot's syndrome. Nuclear β- 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 β-catenin. Exon 3 of β-catenin was sequenced in 6 of the 9 sporadic medulloblastomas with nuclear β-catenin staining. Five of the 6 tumors sequenced had mutations affecting highly conserved β-catenin phosphorylation sites involved in protein stability. These data suggest a simple immunohistochemical method to screen for β-catenin mutations in medulloblastomas.

Original languageEnglish (US)
Pages (from-to)333-337
Number of pages5
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number4
StatePublished - Apr 2000

Fingerprint

Catenins
Medulloblastoma
Mutation
Staining and Labeling
Meningeal Neoplasms
APC Genes
myc Genes
Adenomatous Polyposis Coli
Protein Stability
Growth and Development
Neuroglia
Exons
Signal Transduction
Neoplasms
Cytoplasm
Transcription Factors

Keywords

  • β-Catenin
  • Immunohistochemistry
  • Medulloblastoma
  • Wingless

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Nuclear localization and mutation of β-catenin in medulloblastomas. / Eberhart, Charles G; Tihan, Tarik; Burger, Peter C.

In: Journal of Neuropathology and Experimental Neurology, Vol. 59, No. 4, 04.2000, p. 333-337.

Research output: Contribution to journalArticle

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