Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas

Hui Qi Qu, Karine Jacob, Sarah Fatet, Bing Ge, David Barnett, Olivier Delattre, Damien Faury, Alexandre Montpetit, Lauren Solomon, Peter Hauser, Miklos Garami, Laszlo Bognar, Zoltan Hansely, Robert Mio, Jean Pierre Farmer, Steffen Albrecht, Constantin Polychronakos, Cynthia Hawkins, Nada Jabado

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Available data on genetic events in pediatric grade IV astrocytomas (glioblastoma [pGBM]) are scarce. This has traditionally been a major impediment in understanding the pathogenesis of this tumor and in developing ways for more effective management. Our aim is to chart DNA copy number aberrations (CNAs) and get insight into genetic pathways involved in pGBM. Using the Illumina Infinium Human-1 bead-chip-array (100K single-nucleotide polymorphisms [SNPs]), we genotyped 18 pediatric and 6 adult GBMs. Results were compared to BAC-array profiles harvested on 16 of the same pGBM, to an independent data set of 9 pediatric high-grade astrocytomas (HGAs) analyzed on Affymetrix 250K-SNP arrays, and to existing data sets on HGAs. CNAs were additionally validated by realtime qPCR in a set of genes in pGBM. Our results identify with nonrandom clustering of CNAs in several novel, previously not reported, genomic regions, suggesting that alterations in tumor suppressors and genes involved in the regulation of RNA processing and the cell cycle are major events in the pathogenesis of pGBM. Most regions were distinct from CNAs in aGBMs and show an unexpectedly low frequency of genetic amplification and homozygous deletions and a high frequency of loss of heterozygosity for a high-grade I rapidly dividing tumor. This first, complete, high-resolution profiling of the tumor cell genome fills an important gap in studies on pGBM. It ultimately guides the mapping of oncogenic networks unique to pGBM, identification of the related therapeutic predictors and targets, and development of more effective therapies. It further shows that, despite commonalities in a few CNAs, pGBM and aGBMs are two different diseases.

Original languageEnglish
Pages (from-to)153-163
Number of pages11
JournalNeuro-Oncology
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2010

Keywords

  • Brain tumors
  • LOH
  • Pediatric high-grade astrocytomas
  • SNP arrays

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Qu, H. Q., Jacob, K., Fatet, S., Ge, B., Barnett, D., Delattre, O., Faury, D., Montpetit, A., Solomon, L., Hauser, P., Garami, M., Bognar, L., Hansely, Z., Mio, R., Farmer, J. P., Albrecht, S., Polychronakos, C., Hawkins, C., & Jabado, N. (2010). Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas. Neuro-Oncology, 12(2), 153-163. https://doi.org/10.1093/neuonc/nop001