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Childhood Brain Stem Glioma Treatment (PDQ®)

  • Last Modified: 01/28/2014

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Cellular Classification of Childhood Brain Stem Glioma

Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)



Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)

The genomic characteristics of DIPGs appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. A number of chromosomal abnormalities have been reported for DIPG, including the following:

  • Histone H3 genes: Approximately 80% of DIPG tumors have a mutation in a specific amino acid in one of two histone H3 genes (H3F3A or HIST1H3B).[1] These mutations are less common in non–brain stem pediatric high-grade gliomas and are uncommon in adult high-grade gliomas.[1,2]

  • Receptor tyrosine kinase amplification: PDGFRA amplification occurs in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R).[3,4]

  • P53 deletion: DIPG tumors commonly show deletion of the P53 gene on chromosome 17p.[4]

The gene expression profile of DIPG differs from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas.[4]

References
  1. Wu G, Broniscer A, McEachron TA, et al.: Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44 (3): 251-3, 2012.  [PUBMED Abstract]

  2. Schwartzentruber J, Korshunov A, Liu XY, et al.: Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482 (7384): 226-31, 2012.  [PUBMED Abstract]

  3. Zarghooni M, Bartels U, Lee E, et al.: Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28 (8): 1337-44, 2010.  [PUBMED Abstract]

  4. Paugh BS, Broniscer A, Qu C, et al.: Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29 (30): 3999-4006, 2011.  [PUBMED Abstract]