侵袭性原始神经外胚层脑肿瘤中19号染色体长臂13.41区微小RNA多顺反子的频繁扩增。
Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors.
作者信息
Li Meihua, Lee Kyle F, Lu Yuntao, Clarke Ian, Shih David, Eberhart Charles, Collins V Peter, Van Meter Tim, Picard Daniel, Zhou Limei, Boutros Paul C, Modena Piergiorgio, Liang Muh-Lii, Scherer Steve W, Bouffet Eric, Rutka James T, Pomeroy Scott L, Lau Ching C, Taylor Michael D, Gajjar Amar, Dirks Peter B, Hawkins Cynthia E, Huang Annie
机构信息
Division of Hematology-Oncology, Hospital for Sick Children, Toronto, ON M5G 0A3, Canada.
出版信息
Cancer Cell. 2009 Dec 8;16(6):533-46. doi: 10.1016/j.ccr.2009.10.025.
Abstract
We discovered a high-level amplicon involving the chr19q13.41 microRNA (miRNA) cluster (C19MC) in 11/45 ( approximately 25%) primary CNS-PNET, which results in striking overexpression of miR-517c and 520g. Constitutive expression of miR-517c or 520g promotes in vitro and in vivo oncogenicity, modulates cell survival, and robustly enhances growth of untransformed human neural stem cells (hNSCs) in part by upregulating WNT pathway signaling and restricting differentiation of hNSCs. Remarkably, the C19MC amplicon, which is very rare in other brain tumors (1/263), identifies an aggressive subgroup of CNS-PNET with distinct gene-expression profiles, characteristic histology, and dismal survival. Our data implicate miR-517c and 520g as oncogenes and promising biological markers for CNS-PNET and provide important insights into oncogenic properties of the C19MC locus.
摘要
我们在45例原发性中枢神经系统原始神经外胚层肿瘤（CNS-PNET）中的11例（约25%）中发现了一个涉及19号染色体q13.41微小RNA（miRNA）簇（C19MC）的高水平扩增子，这导致miR-517c和520g显著过表达。miR-517c或520g的组成性表达促进体外和体内致癌性，调节细胞存活，并通过上调WNT信号通路和限制人神经干细胞（hNSC）分化，有力地增强未转化的hNSC生长。值得注意的是，C19MC扩增子在其他脑肿瘤中非常罕见（1/263），它确定了一个具有独特基因表达谱、特征性组织学和较差生存率的侵袭性CNS-PNET亚组。我们的数据表明miR-517c和520g是CNS-PNET的致癌基因和有前景的生物标志物，并为C19MC基因座的致癌特性提供了重要见解。
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