Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin

被引:133
作者
Sharma, Mukesh K.
Mansur, David B.
Reifenberger, Guido
Perry, Arie
Leonard, Jeffrey R.
Aldape, Kenneth D.
Albin, Meredith G.
Emnett, Ryan J.
Loeser, Simon
Watson, Mark A.
Nagarajan, Rakesh
Gutmann, David H.
机构
[1] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO 63110 USA
[5] Univ Dusseldorf, Dept Neuropathol, D-4000 Dusseldorf, Germany
[6] Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
关键词
D O I
10.1158/0008-5472.CAN-06-0973
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pilocytic astrocytomas (PAs) are the most common glioma in children. Whereas many PAs are slow-growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. To identify genetic signatures that might predict PA clinical behavior, we did gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type I (NF1). Whereas no expression signature was found that could discriminate clinically aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Lastly, we also identified a gene expression pattern common to PAs and normal mouse astrocytes and neural stem cells from these distinct brain regions as well as a gene expression pattern shared between PAs and another human glial tumor (ependymoma) arising supratentorially compared with those originating in the posterior fossa. These results suggest that glial tumors share an intrinsic, lineage-specific molecular signature that reflects the brain region in which their nonmalignant predecessors originated.
引用
收藏
页码:890 / 900
页数:11
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