Distinct genetic alterations in pediatric glioblastomas

Abstract

BACKGROUND: Pediatric high-grade tumors, especially glioblastomas (GBs), can be clinically devastating but are under-studied in comparison with adult GBs (aGBs). Molecular features of pediatric GBs (pGBs) are poorly understood and novel-targeted therapies have not been routinely used in pediatric patients with GBs.

METHODS: Twenty-four non-brainstem pGBs were studied. To compare pGBs with aGBs, immunohistochemical staining and fluorescent in situ hybridization were performed in paraffin-embedded tissues. Microarray gene expression analyses were performed in snap-frozen tissues of four primary pGBs, six primary aGBs, and one non-neoplastic brain.

RESULTS: Immunohistochemial p16 loss was more frequent in pGBs, whereas p53, epidermal growth factor receptor, and phosphatase and tensin homolog loss were similar to that of aGBs. No case was isocitrate dehydrogenase (IDH)1 immunopositive or showed the IDH1 R132/IDH2 R172 mutation, suggesting primary GB. Microarray analysis revealed two pGB subtypes (A and B). Type B pGBs and aGBs had similar gene expression profiles; however, the profiles of type A pGBs differed from those of aGBs. In type A pGBs, we identified 90 up- and 63 down-regulated genes; platelet-derived growth factor receptor α polypeptide and CCND2 expression were significantly reduced, whereas they were up-regulated in aGBs.

CONCLUSIONS: Our study found two distinct pGB gene expression profiles: one similar to that of aGBs and the other different. We identified significantly up- and down-regulated genes in pGBs that may provide better targets for diagnostic, prognostic, and therapeutic uses; however, more studies are required to determine the classification and optimal treatment of pediatric patients with GBs.