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Neuro Oncol. 2012 Mar;14(3):326-32. doi: 10.1093/neuonc/nor190. Epub 2011 Nov 7.

Genomic aberrations in pediatric diffuse intrinsic pontine gliomas.

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1
National Cancer Institute, Pediatric Oncology Branch, Pediatric Neuro-Oncology Section, Bldg 10 CRC, Rm 1W-5750, Bethesda, MD 20892-1104, USA. warrenk@mail.nih.gov

Abstract

Diagnostic biopsy is not routinely performed for children with diffuse intrinsic pontine glioma (DIPG). Consequently, our understanding of DIPG biology is hindered by limited tissue availability. We performed comparative genomic hybridization (CGH) on autopsy specimens to examine the feasibility of determining DNA genomic copy number aberrations on formalin-fixed, paraffin-embedded (FFPE) blocks. Histology on FFPE blocks obtained from autopsy of pediatric patients with DIPG was reviewed. Regions were marked for processing, and DNA was extracted from the tissue core, labeled by chemical coupling with Cy5, and hybridized to 105K oligonucleotide CGH arrays. After hybridization and washing, arrays were scanned, and data segmented and processed with Nexus software. Twenty-two samples from 13 subjects were obtained. Histologic variability was noted. CGH was successfully performed on 18 of 22 samples, representing 11 of 13 subjects. All demonstrated DNA copy number abnormalities. High copy number amplification of known oncogenes and homozygous deletions of known tumor suppressor genes were observed. Additional regions of high copy number amplification and homozygous deletion and geographical variations in the CGH patterns were found. CGH performed on FFPE tissue obtained from autopsy yields satisfactory results. This sample set from patients with DIPG was highly informative, with the majority of specimens showing ≥1 abnormality related to a known cancer gene. Aberrations in candidate drug targets were observed. This study establishes the feasibility of genomic DNA analysis from DIPG autopsy material, identifies several targets for which molecular targeted therapy exists, and suggests significant heterogeneity among patients with DIPG.

PMID:
22064882
PMCID:
PMC3280796
DOI:
10.1093/neuonc/nor190
[Indexed for MEDLINE]
Free PMC Article
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