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成神经管细胞瘤的亚型被发现

2018-10-26

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导读:成神经管细胞瘤(成髓细胞瘤)是一种常见类型的儿童脑瘤,被认为主要从小脑形成,其中很多涉及一个涉及“Sonic Hedgehog”的信号通道的异常信号作用。

成神经管细胞瘤(成髓细胞瘤)是一种常见类型的儿童脑瘤,被认为主要从小脑形成,其中很多涉及一个涉及“Sonic Hedgehog”的信号通道的异常信号作用。然而,成神经管细胞瘤之间也有很大的差异性,而且新的研究工作表明,成神经管细胞瘤的一个鲜明的亚型源自“背侧脑干”,与被改变的Wnt信号作用相关。在分子上和临床上弄清不同亚型的特征将有助于今后的治疗工作。这表明,成神经管细胞瘤的不同子类别是本质上不同的疾病,所以治疗策略也可能需要相应地量身打造。(生物谷Bioon.com)

生物谷推荐原文出处:

Nature   doi:10.1038/nature09587

Subtypes of medulloblastoma have distinct developmental origins

Paul Gibson,Yiai Tong,Giles Robinson,Margaret C. Thompson,D. Spencer Currle,Christopher Eden,Tanya A. Kranenburg,Twala Hogg,Helen Poppleton,Julie Martin,David Finkelstein,Stanley Pounds,Aaron Weiss,Zoltan Patay,Matthew Scoggins,Robert Ogg,Yanxin Pei,Zeng-Jie Yang,Sonja Brun,Youngsoo Lee,Frederique Zindy,Janet C. Lindsey,Makoto M. Taketo,Frederick A. Boop,Robert A. Sanford  et al.

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumour subtypes that together comprise the most common malignant childhood brain tumour1, 2, 3, 4. These tumours are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) after aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH subtype)3, 4, 5, 6, 7, 8. The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT subtype)1, 3, 4 arises outside the cerebellum from cells ofthe dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumours infiltrate the dorsal brainstem, whereas SHH-subtype tumours are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence, to our knowledge, that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.

[关键词: 细胞瘤 ]

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