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Advances in Brief

Sporadic Medulloblastomas Contain Oncogenic β-Catenin Mutations

Russell H. Zurawel, Sharon A. Chiappa, Cory Allen and Corey Raffel
Russell H. Zurawel
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Sharon A. Chiappa
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Cory Allen
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Corey Raffel
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DOI:  Published March 1998
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Abstract

The β-catenin, glycogen synthase kinase 3β (GSK-3β), and adenomatous polyposis coli (APC) gene products interact to form a network that influences the rate of cell proliferation. Medulloblastoma occurs as part of Turcot's syndrome, and patients with Turcot's who develop medulloblastomas have been shown to harbor germ-line APC mutations. Although APC mutations have been investigated and not identified in sporadic medulloblastomas, the status of the β-catenin and GSK-3β genes has not been evaluated in this tumor. Here we show that 3 of 67 medulloblastomas harbor β-catenin mutations, each of which converts a GSK-3β phosphorylation site from serine to cysteine. The β-catenin mutation seen in the tumors was not present in matched constitutional DNA in the two cases where matched DNA was available. A loss of heterozygosity analysis of 32 medulloblastomas with paired normal DNA samples was performed with four microsatellite markers flanking the GSK-3β locus; loss of heterozygosity with at least one marker was identified in 7 tumors. Sequencing of the remaining GSK-3β allele in these cases failed to identify any mutations. Taken together, these data suggest that activating mutations in the β-catenin gene may be involved in the development of a subset of medulloblastomas. The GSK-3β gene does not appear to be a target for inactivation in this tumor.

Footnotes

  • ↵1 This work was supported in part by the Pediatric Brain Tumor Foundation of the United States.

  • ↵2 To whom requests for reprints should be addressed, at Department of Neurosurgery, Mayo Clinic and Foundation, 200 First St, SW, Rochester, MN 55905. Phone: (507) 284-3514; Fax: (507) 284-5206; E-mail: raffel.corey@mayo.edu.

  • Received November 12, 1997.
  • Accepted December 31, 1997.
  • ©1998 American Association for Cancer Research.
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March 1998
Volume 58, Issue 5
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Sporadic Medulloblastomas Contain Oncogenic β-Catenin Mutations
Russell H. Zurawel, Sharon A. Chiappa, Cory Allen and Corey Raffel
Cancer Res March 1 1998 (58) (5) 896-899;

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Sporadic Medulloblastomas Contain Oncogenic β-Catenin Mutations
Russell H. Zurawel, Sharon A. Chiappa, Cory Allen and Corey Raffel
Cancer Res March 1 1998 (58) (5) 896-899;
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