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Neuro-Oncology 2008 10(6):995-1003; doi:10.1215/15228517-2008-064
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Copyright 2008 by the Society for Neuro-Oncology

Prevalence of copy-number neutral LOH in glioblastomas revealed by genomewide analysis of laser-microdissected tissues

Daisuke Kuga, Masahiro Mizoguchi, Yanlei Guan, Nobuhiro Hata, Koji Yoshimoto, Tadahisa Shono, Satoshi O. Suzuki, Yoji Kukita, Tomoko Tahira, Shinji Nagata, Tomio Sasaki and Kenshi Hayashi

Department of Neurosurgery (D.K., M.M., Y.G., N.H., K.Y., T.Sh., S.N., T.Sa.) and Department of Neuropathology (S.O.S.), Graduate School of Medical Sciences, and Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation (D.K., Y.G., Y.K., T.T., K.H.), Kyushu University, Fukuoka, Japan

Address correspondence to Kenshi Hayashi, Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan (khayashi{at}gen.kyushu-u.ac.jp).


  Abstract

We have employed a laser-capture microdissection technique and single-nucleotide polymorphism arrays to characterize genomic alterations associated with the development of glioblastoma multiforme (GBM). Combined analysis of loss of heterozygosity (LOH) and copy number revealed that more than half (56.3%) of the 254 identified LOH loci showed no copy-number alteration, indicating the presence of copy-number neutral LOH (cnLOH). Furthermore, we found a GBM case that showed cnLOH in 18 of the 22 autosomes. These results were confirmed by quantitative real-time PCR, microsatellite analysis, and fluorescence in situ hybridization. The high rate of cnLOH suggests that epigenetic abnormalities of many genes are involved in the development and progression of GBMs.

Keywords: copy-number alteration, copy-number neutral LOH, glioblastoma, loss of heterozygosity, single-nucleotide polymorphism array

Received October 10, 2007; Accepted July 8, 2008


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