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Child's Nervous System

, Volume 28, Issue 7, pp 1025–1032 | Cite as

Distinct genetic alterations in pediatric glioblastomas

  • Sun-ju Byeon
  • Jae Kyung Myung
  • Se Hoon Kim
  • Seung-Ki Kim
  • Ji Hoon Phi
  • Sung-Hye ParkEmail author
Original Paper

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.

Keyword

Glioblastoma Pediatrics Molecular pathology Gene expression profile 

Notes

Acknowledgments

This research was supported by Basic Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0003666).

Conflict of interest

We have no conflicts of interest to declare.

Supplementary material

381_2012_1773_MOESM1_ESM.doc (310 kb)
ESM 1 (DOC 310 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Sun-ju Byeon
    • 1
  • Jae Kyung Myung
    • 2
  • Se Hoon Kim
    • 3
  • Seung-Ki Kim
    • 4
  • Ji Hoon Phi
    • 5
  • Sung-Hye Park
    • 6
    Email author
  1. 1.Department of PathologySeoul Nation University HospitalSeoulRepublic of Korea
  2. 2.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of PathologyYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Division of Pediatric NeurosurgerySeoul National University Children’s Hospital, Seoul National University College of MedicineSeoulRepublic of Korea
  5. 5.Department of NeurosurgerySeoul National University, College of MedicineSeoulRepublic of Korea
  6. 6.Department of Pathology, and Neuroscience Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea

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