Unique molecular characteristics of radiation-induced glioblastoma.
Radiation-induced glioblastomas (RIGs) represent a significant proportion of glioblastomas (GBMs) seen in children and young adults and manifest poor prognosis. Little is known about their underlying biology, although limited studies have suggested no unique histologic or cytogenetic characteristics to distinguish them from de novo GBMs. In this study, we confirmed that a series of 5 RIGs showed no unique histologic or cytogenetic features compared with de novo pediatric GBMs, prompting us to further investigate RIGs using gene expression microarray profiling and Western blot analysis. Despite the inability of histologic and molecular genetic studies to identify distinguishing features between RIGs and pediatric GBMs, gene microarrays suggested significant differences between these 2 tumor types, at least those occurring in pediatric patients. Pediatric RIGs show greater homogeneity of gene expression than do de novo pediatric GBMs. Greater overlap was detected in gene expression patterns between RIGs and pilocytic astrocytomas than between RIGs and GBMs, medulloblastomas, ependymomas, atypical teratoid rhabdoid tumors, or rhabdomyosarcomas, suggesting a common precursor cell for RIG and pilocytic astrocytoma. Western blot analyses confirmed that ErbB3, Sox10, and platelet-derived growth factor receptor-alpha proteins were consistently expressed in RIGs but rarely in pediatric GBMs.
Donson
Andrew M
AM
Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA. andrew.donson@uchsc.edu
Erwin
Nicole S
NS
Kleinschmidt-DeMasters
B K
BK
Madden
Jennifer R
JR
Addo-Yobo
Steven O
SO
Foreman
Nicholas K
NK
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000556:secondary*; D006801:Humans; D008297:Male; D009381:Neoplasms, Radiation-Induced; D011827:Radiation