Kuga Daisuke, Mizoguchi Masahiro, Guan Yanlei, Hata Nobuhiro, Yoshimoto Koji, Shono Tadahisa, Suzuki Satoshi O, Kukita Yoji, Tahira Tomoko, Nagata Shinji, Sasaki Tomio, Hayashi Kenshi
Department of Neurosurgery, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Neuro Oncol. 2008 Dec;10(6):995-1003. doi: 10.1215/15228517-2008-064. Epub 2008 Aug 12.
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.
我们采用了激光捕获显微切割技术和单核苷酸多态性阵列来表征与多形性胶质母细胞瘤（GBM）发生相关的基因组改变。对杂合性缺失（LOH）和拷贝数的联合分析显示，在254个鉴定出的LOH位点中，超过一半（56.3%）未显示拷贝数改变，表明存在拷贝数中性的LOH（cnLOH）。此外，我们发现1例GBM病例在22条常染色体中的18条上显示出cnLOH。这些结果通过定量实时PCR、微卫星分析和荧光原位杂交得到了证实。cnLOH的高发生率表明许多基因的表观遗传异常参与了GBM的发生和发展。
