Expression of the c-Myc protein in childhood medulloblastoma

J Pediatr Hematol Oncol. Jan-Feb 1998;20(1):18-25. doi: 10.1097/00043426-199801000-00003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Genes, myc
  • Humans
  • Medulloblastoma / chemistry*
  • Medulloblastoma / genetics
  • Proto-Oncogene Proteins c-myc / analysis*
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger