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Am J Cancer Res. 2014 May 26;4(3):293-303. eCollection 2014.

Genome-wide copy number analysis in pediatric glioblastoma multiforme.

Author information

  • 1Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy.
  • 2Neuro-Oncology Unit, Department of Pediatrics, Meyer Children's Hospital Florence, Italy.
  • 3Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence Florence, Italy.
  • 4Department of Clinical and Experimental Medicine, University of Florence Florence, Italy.
  • 5Department of Clinical and Experimental Medicine, University of Florence Florence, Italy ; Laboratory of Molecular Genetics, G. Gaslini Institute Genova, Italy.
  • 6Department of Molecular Medicine, University of Pavia Pavia, Italy.
  • 7Anatomic Pathology Unit, Meyer Children's University Hospital Florence, Italy.
  • 8Neurosurgery Unit, Department of Neuroscience, Meyer Children's Hospital Florence, Italy.
  • 9Department of Health Sciences, University of Florence Florence, Italy.
  • 10Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy ; Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence Florence, Italy ; FiorGen Foundation for Pharmacogenomics Sesto Fiorentino, Italy.

Abstract

Glioblastoma (GBM) is a very aggressive and lethal brain tumor with poor prognosis. Despite new treatment strategies, patients' median survival is still less than 1 year in most cases. Few studies have focused exclusively on this disease in children and most of our understanding of the disease process and its clinical outcome has come from studies on malignant gliomas in childhood, combining children with the diagnosis of GBM with other pediatric patients harboring high grade malignant tumors other than GBM. In this study we investigated, using array-CGH platforms, children (median age of 9 years) affected by GBM (WHO-grade IV). We identified recurrent Copy Number Alterations demonstrating that different chromosome regions are involved, in various combinations. These observations suggest a condition of strong genomic instability. Since cancer is an acquired disease and inherited factors play a significant role, we compared for the first time the constitutional Copy Number Variations with the Copy Number Alterations found in tumor biopsy. We speculate that genes included in the recurrent 9p21.3 and 16p13.3 deletions and 1q32.1-q44 duplication play a crucial role for tumorigenesis and/or progression. In particular we suggest that the A2BP1 gene (16p13.3) is one possible culprit of the disease. Given the rarity of the disease, the poor quality and quantity of bioptic material and the scarcity of data in the literature, our findings may better elucidate the genomic background of these tumors. The recognition of candidate genes underlying this disease could then improve treatment strategies for this devastating tumor.

KEYWORDS:

Pediatric glioblastoma multiforme; amplification; array-CGH; central nervous tumor; copy number alterations (CNA); copy number variations (CNVs); deletion; duplication; minimum common regions; tumorigenesis

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