c-Myc promoter activation in medulloblastoma

%The c-myc oncogene is commonly activated in medulloblastoma. Genomic amplification is a well-documented cause of c-myc activation but does not account for all cases of c-myc activation. In this study, we sought other means by which c-myc is overexpressed in medulloblastoma. Twelve medulloblastoma or PNET cell lines were screened for c-myc genomic amplification, mRNA levels, and protein levels. Two medulloblastoma lines, D283 Med and D721 Med, were identified that expressed c-myc mRNA and protein at high levels without genomic amplification. The c-myc gene's regulatory sequences were normal in those cell lines. However, specific regions of the promoter, independent of the beta-catenin binding sites, were responsible for activation as revealed by promoter assays and site-directed mutagenesis. Transcriptional activation by a beta-catenin-independent pathway is therefore a likely mechanism for c-myc overexpression in a subset of medulloblastomas.