© Copyright 2008 by the Society for Neuro-Oncology
Received October 10, 2007
Accepted June 12, 2008
Basic and Translational Investigations
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Prevalence of copy number neutral LOH in glioblastomas revealed by genome-wide analysis of laser-microdissected tissues
Daisuke Kuga 1,
Masahiro Mizoguchi 2,
Yanlei Guan 1,
Nobuhiro Hata 3,
Koji Yoshimoto 4,
Tadahisa Shono 4,
Satoshi O. Suzuki 5,
Yoji Kukita 6,
Tomoko Tahira 6,
Shinji Nagata 4,
Tomio Sasaki 4,
Kenshi Hayashi 7*
1 Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582; 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
2 Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
3 Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
4 Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
5 Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan
6 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
7 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
* To whom correspondence should be addressed. E-mail: khayashi{at}gen.kyushu-u.ac.jp.
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Abstract |
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We have employed a laser capture microdissection technique and single nucleotide polymorphism arrays to characterize genomic alterations associated with the development of glioblastomas. Combined analysis of loss of heterozygosity (LOH) and copy number revealed that more than half (56.3%) of the identified 254 LOH loci showed no copy number alteration, indicating the presence of copy number neutral LOH. Furthermore, we found a glioblastoma case which showed copy number neutral LOH in 18 of the 22 autosomes. These results were confirmed by quantitative real-time PCR, microsatellite analysis, and fluorescence in situ hybridization (FISH). The high rate of copy number neutral LOH suggests that epigenetic abnormally of many genes are involved in the development and progression of glioblastomas.
Key Words:
copy number alteration, glioblastoma, loss of heterozygosity, single nucleotide polymorphism array, copy number neutral LOH
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