Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes
Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes
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DOI：
10.1007/s00401-008-0467-y
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发表时间：
2009-04-01
影响因子：
12.7
通讯作者：
Korshunov, Andrey
中科院分区：
文献类型：
--
作者：
Pfister, Stefan;Remke, Marc;Korshunov, Andrey
具有丰富神经胶质细胞和真神经胶质细胞的胚胎性肿瘤（ETANTR）包括通常发生在婴儿中的胚胎性脑肿瘤的罕见变体。迄今为止，文献中仅报道了13例，对这些肿瘤的分子发病机制知之甚少。在这里，我们描述了一个2岁的女孩ETANTR的情况下，提出了一个大肿瘤在小脑蚓部。组织学检查显示成簇的小未分化细胞，包括室管膜样细胞，混合有大的纤维状和少细胞神经纤维样区域，指示ETANTR。基因组不平衡检测使用基于阵列的比较基因组杂交。除了先前在ETANTR中描述的2号染色体三体之外，阵列CGH还显示了染色体带19q13.42处0.89 Mb的高水平基因组扩增，覆盖了一个microRNA簇和几个蛋白质编码基因。迄今为止，这种畸变尚未在任何其他脑肿瘤中描述，表明ETANTR中存在特异性畸变。与正常小脑或全脑相比，19q13.42处的microRNA簇中包含的microRNA（包括oncomirs miRNA-372和miRNA-373）在肿瘤中高度上调。总之，这是第一份关于ETANTR中潜在特异性遗传畸变的报告，支持了不同肿瘤实体的假设。
Embryonal tumors with abundant neuropil and true rosettes (ETANTR) comprise a rare variant of embryonal brain tumors usually occurring in infants. Only 13 cases have been reported in the literature to date and little is known about the molecular pathogenesis of these tumors. Here, we describe a case of ETANTR in a 2-year-old girl presenting with a large tumor in the vermis of the cerebellum. Histological examination showed clusters of small-undifferentiated cells including ependymoblastic-like rosettes admixed with large fibrillar and paucicellular neuropil-like areas indicative for ETANTR. Genomic imbalances were detected by using array-based comparative genomic hybridization. In addition to trisomy of chromosome 2, which has been previously described in ETANTR, array-CGH revealed high-level genomic amplification of 0.89 Mb at chromosome band 19q13.42 covering a microRNA cluster and several protein-coding genes. This aberration has not been described in any other brain tumor to date, indicating a specific aberration in ETANTR. MicroRNAs contained in the microRNA cluster at 19q13.42 including oncomirs miRNA-372 and miRNA-373 were highly up-regulated in the tumor when compared to normal cerebellum or whole brain. In summary, this is the first report on a potentially specific genetic aberration in ETANTR, supporting the hypothesis of a distinct tumor entity.