EXPRESSION OF THE C-MYC PROTEIN IN CHILDHOOD MEDULLOBLASTOMA

Purpose: The purpose of this study was to determine the incidence of c -Myc protein expression in medulloblastoma/primititive neuroectodermal tumor (MB/PNET) and to identify mechanisms in addition to c-myc gene amplification that lead to increased protein expression. Methods: We a nalyzed 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 tu mor specimens and cell lines using immunohistochemical staining with a c-Myc-specific monoclonal antibody. Results: Southern analysis confir med c-myc gene amplification in the D425 MED cell line and re-arrangem ent 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 w ere dramatically elevated in both lines. Using a c-myc probe, fluoresc ence in situ hybridization (FISH) showed c-myc present in 3 tandem cop ies at 8q24 in D283 MED and multiple copies as double minutes in D425 MED. Immunohistochemistry showed c-Myc protein expression in 9 of 10 t umors and all cell lines, regardless of gene amplification status or l evel of mRNA expression. Conclusions: c-Myc protein expression is comm on 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 s tudies support a role for c-Myc in the development of this common chil dhood tumor.