title: Genome-wide copy number analysis in pediatric glioblastoma multiforme.
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.
authors: Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy.
authors: Laura
authors: L
authors: Giunti
authors: Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy.
authors: Marilena
authors: M
authors: Pantaleo
authors: Neuro-Oncology Unit, Department of Pediatrics, Meyer Children's Hospital Florence, Italy.
authors: Iacopo
authors: I
authors: Sardi
authors: Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence Florence, Italy.
authors: Aldesia
authors: A
authors: Provenzano
authors: Department of Clinical and Experimental Medicine, University of Florence Florence, Italy.
authors: Alberto
authors: A
authors: Magi
authors: Neuro-Oncology Unit, Department of Pediatrics, Meyer Children's Hospital Florence, Italy.
authors: Stefania
authors: S
authors: Cardellicchio
authors: Department of Clinical and Experimental Medicine, University of Florence Florence, Italy.
authors: Francesca
authors: F
authors: Castiglione
authors: Department of Clinical and Experimental Medicine, University of Florence Florence, Italy ; Laboratory of Molecular Genetics, G. Gaslini Institute Genova, Italy.
authors: Lorenzo
authors: L
authors: Tattini
authors: Department of Molecular Medicine, University of Pavia Pavia, Italy.
authors: Francesca
authors: F
authors: Novara
authors: Anatomic Pathology Unit, Meyer Children's University Hospital Florence, Italy.
authors: Anna Maria
authors: AM
authors: Buccoliero
authors: Neurosurgery Unit, Department of Neuroscience, Meyer Children's Hospital Florence, Italy.
authors: Maurizio
authors: M
authors: de Martino
authors: Department of Health Sciences, University of Florence Florence, Italy.
authors: Lorenzo
authors: L
authors: Genitori
authors: Department of Molecular Medicine, University of Pavia Pavia, Italy.
authors: Orsetta
authors: O
authors: Zuffardi
authors: Medical 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.
authors: Sabrina
authors: S
authors: Giglio
keywords: Pediatric glioblastoma multiforme; amplification; array-CGH; central nervous tumor; copy number alterations (CNA); copy number variations (CNVs); deletion; duplication; minimum common regions; tumorigenesis