Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes.
Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes.
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DOI：
10.1016/j.ccell.2015.09.007
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发表时间：
2015-10-12
期刊：
影响因子：
50.3
通讯作者：
Parada LF
中科院分区：
文献类型：
--
作者：
Alcantara Llaguno SR;Wang Z;Sun D;Chen J;Xu J;Kim E;Hatanpaa KJ;Raisanen JM;Burns DK;Johnson JE;Parada LF
多形性胶质母细胞瘤（GBM）研究的一个中心问题是肿瘤起始细胞的身份，以及它对恶性表型和基因组状态的贡献。我们利用中枢神经系统（CNS）祖细胞特异性诱导Cre小鼠突变Nf1、Trp53和Pten，研究成年谱系限制性祖细胞诱导完全渗透GBM的潜力。我们确定了两种表型和分子上不同的GBM亚型，由相同的驱动突变控制。我们证明这两种亚型起源于功能独立的成年中枢神经系统祖细胞群。尽管在组织学上与GBM相同，但根据肿瘤起始细胞的谱系，这些肿瘤类型是可分离的。这些研究指出，细胞起源是GBM亚型多样性的主要决定因素。
A central question in glioblastoma multiforme (GBM) research is the identity of the tumor-initiating cell, and its contribution to the malignant phenotype and genomic state. We examine the potential of adult lineage restricted progenitors to induce fully penetrant GBM using central nervous system (CNS) progenitor-specific inducible Cre mice to mutate Nf1, Trp53 and Pten. We identify two phenotypically and molecularly distinct GBM subtypes governed by identical driver mutations. We demonstrate that the two subtypes arise from functionally independent pools of adult CNS progenitors. Despite histologic identity as GBM, these tumor types are separable based on the lineage of the tumor-initiating cell. These studies point to the cell of origin as a major determinant of GBM subtype diversity.