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.
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.
Authors: Larry L Wang; Rie Suganuma; Naohiko Ikegaki; Xao Tang; Arlene Naranjo; Patrick McGrady; Wendy B London; Michael D Hogarty; Julie M Gastier-Foster; A Thomas Look; Julie R Park; John M Maris; Susan L Cohn; Robert C Seeger; Hiroyuki Shimada Journal: Cancer Date: 2013-07-30 Impact factor: 6.860
Authors: M C Frühwald; M S O'Dorisio; L J Rush; J L Reiter; D J Smiraglia; G Wenger; J F Costello; P S White; R Krahe; G M Brodeur; C Plass Journal: J Med Genet Date: 2000-07 Impact factor: 6.318
Authors: Prasenjit Das; Tarun Puri; Vaishali Suri; M C Sharma; B S Sharma; Chitra Sarkar Journal: Childs Nerv Syst Date: 2009-05-15 Impact factor: 1.475
Authors: Judith M de Bont; Roger J Packer; Erna M Michiels; Monique L den Boer; Rob Pieters Journal: Neuro Oncol Date: 2008-08-01 Impact factor: 12.300