In English | En español
Questions About Cancer? 1-800-4-CANCER

Childhood Brain Stem Glioma Treatment (PDQ®)

  • Last Modified: 05/19/2014

Page Options

  • Print This Page
  • Print This Document
  • View Entire Document
  • Email This Document

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 and genomic 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 the histone H3.1 (H3F3A) or H3.3 (HIST1H3B) genes.[1-5] These same mutations are observed in pediatric high-grade gliomas at other midline locations but are uncommon in cortical pediatric high-grade gliomas and in adult high-grade gliomas.[1-6]

  • Activin A receptor, type I (ACVR1) gene: Approximately 20% of DIPG cases have activating mutations in the ACVR1 gene, with most occurring concurrently with H3.3 mutations.[2-5] Germline mutations in ACVR1 cause the autosomal dominant syndrome fibrodysplasia ossificans progressiva (FOP), although there is no cancer predisposition in FOP.[7]

  • 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).[8,9]

  • TP53 deletion: DIPG tumors commonly show deletion of the TP53 gene on chromosome 17p.[9] Additionally, TP53 is commonly mutated in DIPG tumors, particularly those with histone H3 gene mutations.[2-5,10] Aneuploidy is commonly observed in cases with TP53 mutations.[5]

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.[9]

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. Wu G, Diaz AK, Paugh BS, et al.: The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46 (5): 444-50, 2014.  [PUBMED Abstract]

  3. Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, et al.: Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet 46 (5): 462-6, 2014.  [PUBMED Abstract]

  4. Taylor KR, Mackay A, Truffaux N, et al.: Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46 (5): 457-61, 2014.  [PUBMED Abstract]

  5. Buczkowicz P, Hoeman C, Rakopoulos P, et al.: Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46 (5): 451-6, 2014.  [PUBMED Abstract]

  6. 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]

  7. Shore EM, Xu M, Feldman GJ, et al.: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 38 (5): 525-7, 2006.  [PUBMED Abstract]

  8. 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]

  9. 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]

  10. Khuong-Quang DA, Buczkowicz P, Rakopoulos P, et al.: K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124 (3): 439-47, 2012.  [PUBMED Abstract]