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Control of β‐catenin/Tcf‐directed transcription in medulloblastoma
Author(s) -
Raffel C
Publication year - 2004
Publication title -
acta pædiatrica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 115
eISSN - 1651-2227
pISSN - 0803-5253
DOI - 10.1111/j.1651-2227.2004.tb03049.x
Subject(s) - medulloblastoma , adenomatous polyposis coli , cancer research , genetics , gene , biology , gsk 3 , loss of heterozygosity , catenin , beta catenin , microbiology and biotechnology , allele , wnt signaling pathway , medicine , phosphorylation , cancer , colorectal cancer
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 syndrome, who develop medulloblastomas, have been shown to harbor germline APC mutations. While 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. This study shows 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 2 cases where matched normal DNA was available. A loss of heterozygosity (LOH) analysis of 32 medulloblastomas with paired normal DNA samples was performed with 4 microsatellite markers flanking the GSK‐3β locus; LOH 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.