High-resolution global genomic survey of 178 gliomas reveals novel regions of copy number alteration and allelic imbalances

被引:90
作者
Kotliarov, Yuri
Steed, Mary Ellen
Christopher, Neil
Walling, Jennifer
Su, Qin
Center, Angela
Heiss, John
Rosenblum, Mark
Mikkelsen, Tom
Zenklusen, Jean C.
Fine, Howard A.
机构
[1] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA
[2] NINDS, NIH, Bethesda, MD 20892 USA
[3] Henry Ford Hosp, Dept Neurol, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA
[4] Henry Ford Hosp, Dept Neurosurg, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA
关键词
D O I
10.1158/0008-5472.CAN-06-1691
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Primary brain tumors are the fourth leading cause of cancer mortality in adults under the age of 54 years and the leading cause of cancer mortality in children in the United States. Therapy for the most common type of primary brain tumors, gliomas, remains suboptimal. The development of new and more effective treatments will likely require a better understanding of the biology of these tumors. Here, we show that use of the high-density 100K single-nucleotide polymorphism arrays in a large number of primary tumor samples allows for a much higher resolution survey of the glioma genome than has been previously reported in any tumor type. We not only confirmed alterations in genomic areas previously reported to be affected in gliomas, but we also refined the location of those sites and uncovered multiple, previously unknown regions that are affected by copy number alterations (amplifications, homozygous and heterozygous deletions) as well as allelic imbalances (loss of heterozygosity/gene conversions). The wealth of genomic data produced may allow for the development of a more rational molecular classification of gliomas and serve as an important starting point in the search for new molecular therapeutic targets.
引用
收藏
页码:9428 / 9436
页数:9
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