Genetic Alteration of Pediatric Glioblastomas.
Jahee Seo, Jae Kyung Myung, Sun-Ju Byun, Se Hoon Kim, Sung-Hye Park. Seoul National University Hospita, Korea; Yonsei University Hospital, Seoul, Korea
Background: Pediatric high grade glioma (HGG) is a relatively under-studied tumor of the central nervous system. They are highly invasive tumors with poor response to conventional treatment. Although they are morphologically similar to HGGs of other age groups, some authors insisted that the WHO classification system may not be accurately representative of the histopathological diversity of the childhood brain tumors. Unlike those in adults, the tumorigenesis of HGG in children remained poorly understood partly due to the limited availability of suitable models or cell lines.
Design: Twenty five cases of non-brainstem primary GBMs obtained from two hospitals namely, Seoul National University Hospital and Yonsei University Hospital from 1989 to 2009 were used. Gene expression profiling studies was done using Illumina Human HT-12 v3 gene Expression Bead Chip (Illumina, Inc., San Diego, CA) that contained 48,804 developmental and cancer genes. Materials were mRNA extracted from 4 childhood and 6 adults GBMs and one case of nonneoplastic child brain, which were fresh frozen tissue.
Results: Of the 25 cases, p53 overexpression was found in 25.9% and loss of p16 and PTEN expression were noted in 61.5% and 25.9%, respectively. Immunohistochemistry with EGFR and EGFRvIII (Zymed) revealed overexpression of the proteins in 40% and 61.5%, respectively but EGFR gene amplification and high polysomy by fluorescence-in-situ hybridization were only observed in 25.9%. 1p and 19q deletion was present in 8% and 4%, respectively. CD133 was positive in 32 %. Using non hierarchical clustering analysis, we found that two pediatric GBMs from younger age group (8 and 9 years old) possessed different genetic profile compared to two others that belonged to a relatively older age groups (11 and 13 years old) and the adult GBMs. In the cases from the younger age group, we identified 24 up-regulated and 40 down-regulated genes. The most significantly up-regulated genes among these were TNFRSF14, ELF4, and some mRNA of RRAD. The genes that were down regulated were Cyclin D2, Neurocan, phosphodiesterase 4B, OLIG1, etc.
Conclusions: In conclusion, the EGFRvIII overexpression and p16 loss were more frequent findings in pediatric GBMs than in adult GBMs. However, in other parameter such as p53, EGFR overexpression and PTEN loss were just comparable between the two groups of neoplasms. Pediatric GBMs in children less than 10 years old have different gene expression profile from those in the older child and adult GBMs suggesting that different molecular pathways may exist in this group of neoplasm.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 229, Tuesday Afternoon