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Gerges N, Fontebasso AM, Albrecht S, et al. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm. Genome Med. 2013;5(7):66doi: 10.1186/gm470.
Gerges, N., Fontebasso, A. M., Albrecht, S., Faury, D., & Jabado, N. (2013). Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm. Genome medicine, 5(7), 66. https://doi.org/10.1186/gm470
Gerges, Noha, et al. "Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm." Genome medicine vol. 5,7 (2013): 66. doi: https://doi.org/10.1186/gm470
Gerges N, Fontebasso AM, Albrecht S, Faury D, Jabado N. Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm. Genome Med. 2013 Jul 30;5(7):66. doi: 10.1186/gm470. eCollection 2013. PMID: 23906214; PMCID: PMC3979088.
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Genome Med. 2013 Jul 30;5(7):66. doi: 10.1186/gm470. eCollection 2013.

Pediatric high-grade astrocytomas: a distinct neuro-oncological paradigm.

Genome medicine

Noha Gerges, Adam M Fontebasso, Steffen Albrecht, Damien Faury, Nada Jabado

Affiliations

  1. Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada, H3Z2Z3.
  2. Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, Canada, H3Z2Z3.
  3. Department of Pathology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada, H3H1P3.
  4. Departments of Pediatrics and Human Genetics, McGill University and McGill University Health Centre, Montreal, Quebec, Canada, H3Z2Z3 ; Division of Experimental Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, Canada, H3Z2Z3.

PMID: 23906214 PMCID: PMC3979088 DOI: 10.1186/gm470

Abstract

Brain tumors are the leading cause of cancer-related death in children. High-grade astrocytomas (HGAs), in particular, are lethal in children across all ages. Integrative genome-wide analyses of the tumor's genome, transcriptome and epigenome, using next-generation sequencing technologies and genome-wide DNA methylation arrays, have provided valuable breakthroughs in our understanding of the pathogenesis of HGAs across all ages. Recent profiling studies have provided insight into the epigenetic nature of gliomas in young adults and HGAs in children, particularly with the identification of recurrent gain-of-function driver mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) and the epigenetic influence of their oncometabolite 2-hydroxyglutarate, as well as mutations in the histone 3 variant 3 gene (H3F3A) and loss-of-function mutations in the histone 3 lysine 36 trimethyltransferase gene (SETD2). Mutations in H3F3A result in amino acid substitutions at residues thought to directly (K27M) or indirectly (G34R/V) affect histone post-translational modifications, suggesting they have the capacity to affect the epigenome in a profound manner. Here, we review recent genomic studies, and discuss evidence supporting the molecular characterization of pediatric HGAs to complement traditional approaches, such as histology of resected tumors. We also describe newly identified molecular mechanisms and discuss putative therapeutic approaches for HGAs specific to pediatrics, highlighting the necessity for the evolution of HGA disease management approaches.

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