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Background: Amplification of the N-myc oncogene is associated with adverse outcomes in the common childhood tumor, neuroblastoma. Because the transforming properties of Myc are related to its ability to modulate gene expression, the authors used cDNA microarrays to identify potential Myc target genes., Methods: Expression levels of 4608 genes were analyzed in a series of neuroblastoma cell lines. Identical analyses were performed in a panel of medulloblastoma cell lines to identify c-Myc targets and to determine the extent to which N-Myc targets and c-Myc targets were shared. Comparisons were made between cell lines with high levels versus low levels of Myc protein expression., Results: Array analyses yielded 121 genes with increased expression levels (>or= 1.65-fold) and 9 genes with decreased expression levels in N-Myc-expressing versus nonexpressing cell lines. Many of these were newly identified targets of biologic interest. Fifty percent of the N-Myc targets (60 of 121) were mutual c-Myc targets. A significant correlation between the level of N-myc and selected target gene expression was demonstrated independently in 27 neuroblastoma tumor samples and in an N-myc-inducible cell line system., Conclusions: A number of diverse pathways are modulated by N-Myc in neuroblastoma. Although, overall, there was significant correlation between myc and target transcript expression among cohorts of tumors, great variability in levels of target expression was seen among individual tumor samples, and this biologic heterogeneity in the levels of target gene expression may offer insight into differences in the clinical behavior of neuroblastoma and may prove to be of prognostic significance in the future., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11584)

Purpose: The purpose of this study was to determine the incidence of c-Myc protein expression in medulloblastoma/primitive neuroectodermal tumor (MB/PNET) and to identify mechanisms in addition to c-myc gene amplification that lead to increased protein expression., Methods: We analyzed c-myc gene copy number, mRNA level and protein expression in a panel of MB/PNET cell lines. C-Myc protein levels were assessed in tumor specimens and cell lines using immunohistochemical staining with a c-Myc-specific monoclonal antibody., Results: Southern analysis confirmed c-myc gene amplification in the D425 MED cell line and re-arrangement of one allele in D283 MED, which was analyzed further and appeared to represent a small deletion 3' of exon 3. C-myc transcript levels were dramatically elevated in both lines. Using a c-myc probe, fluorescence in situ hybridization (FISH) showed c-myc present in 3 tandem copies at 8q24 in D283 MED and multiple copies as double minutes in D425 MED. Immunohistochemistry showed c-Myc protein expression in 9 of 10 tumors and all cell lines, regardless of gene amplification status or level of mRNA expression., Conclusions: c-Myc protein expression is common in MB/PNET tumor specimens and cell lines. Elevated protein levels are observed in the absence of amplification, suggesting that multiple mechanisms of c-myc dysregulation may be involved in MB/PNET. These studies support a role for c-Myc in the development of this common childhood tumor.