Exomic Sequencing of Four Rare Central Nervous System Tumor Types
Exomic Sequencing of Four Rare Central Nervous System Tumor Types
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DOI：
10.18632/oncotarget.964
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发表时间：
2013-04-01
期刊：
影响因子：
--
通讯作者：
Papadopoulos, Nickolas
中科院分区：
文献类型：
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作者：
Bettegowda, Chetan;Agrawal, Nishant;Papadopoulos, Nickolas
中枢神经系统（CNS）的罕见肿瘤的异质人群引起显著的发病率和死亡率。为了探索其遗传起源，我们对12例多形性黄色星形细胞瘤（PXA）、17例非脑干儿童胶质母细胞瘤（PGBM）、8例颅内室管膜瘤（IEP）和8例脊髓室管膜瘤（SCEP）的外显子组进行了测序。突变谱分析显示，在四种肿瘤类型中，主要的单碱基对取代是C: G>T: a转变。我们的数据证实了几个已知驱动基因在中枢神经系统肿瘤中的关键作用，包括PGBM中的TP53和ATRX，以及sps中的NF2。此外，我们发现激活BRAF突变在低级别和高级别胶质细胞肿瘤中都起着核心作用。此外，在33%的PXA患者中发现了哺乳动物雷帕霉素靶蛋白（mTOR）通路成员编码基因的改变。我们的研究支持这样一种假设，即病理相似的肿瘤发生在不同的年龄组和不同的室室，可能代表不同的疾病过程和不同的遗传组成。
A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric glioblastomas (PGBM), 8 intracranial ependymomas (IEP) and 8 spinal cord ependymomas (SCEP). Analysis of the mutational spectra revealed that the predominant single base pair substitution was a C: G>T: A transition in each of the four tumor types. Our data confirm the critical roles of several known driver genes within CNS neoplasms, including TP53 and ATRX in PGBM, and NF2 in SCEPs. Additionally, we show that activating BRAF mutations play a central role in both low and high grade glial tumors. Furthermore, alterations in genes coding for members of the mammalian target of rapamycin (mTOR) pathway were observed in 33% of PXA. Our study supports the hypothesis that pathologically similar tumors arising in different age groups and from different compartments may represent distinct disease processes with varied genetic composition.