Glioblastoma multiforme in an Asian population: evidence for a distinct genetic pathway.
In Singapore astrocytic tumours occur in only 25% of patients with primary brain tumours compared to 40-60% in other series. Glioblastoma multiforme arises either de novo as a primary glioblastomas associated with epidermal growth factor receptor (EGFR) and mdm2 over-expression or as a secondary glioblastomas, through malignant progression from low-grade astrocytomas, associated with p53 mutations and PDGFR-alpha over-expression. Using immunohistochemical methods and DNA sequencing, we studied our population of glioblastomas for overexpression of EGFR, mdm2, p53, and PDGFR-alpha as well directly for mutations of the p53 gene. While levels of over-expression of EGFR and mdm2 were consistent with levels expected for primary glioblastomas, levels of p53 and PDGFR-alpha were consistent with levels documented for secondary glioblastomas. Notably 96% of the samples over-expressed p53 as detected with monoclonal antibody pAb 240. Of the 39 samples available for DNA sequencing 18% (7/39) had p53 mutations, including three mutations previously undocumented in glioblastomas. These results provide strong evidence that glioblastomas in Asian patients do not conform to currently accepted models of glioblastoma development, and that clinically defined glioblastomas in these patients show genetic changes consistent with both 'primary' and 'secondary' glioblastomas.
Das
Asha
A
Department of Neurology, National Neuroscience Institute, Singapore.
Tan
Wan-Loo
WL
Teo
Jennifer
J
Smith
Duncan R
DR
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000208:ethnology / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005909:Glioblastoma / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha