Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease.
Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease.
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DOI：
10.1038/modpathol.2011.61
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发表时间：
2011-08
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影响因子：
--
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中科院分区：
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越来越多的证据表明，肿瘤抑制基因功能的敲除导致发育停滞和细胞分化的延长。在周围神经系统的肿瘤抑制基因疾病，冯希佩尔-林道病的患者，我们已经证明了发育停滞的结构元素组成的成血管祖细胞。一些发育停滞的结构元素发展成一个坦率的肿瘤，血管母细胞瘤。然而，在von Hippel-Lindau病中，成血管细胞瘤经常在小脑中观察到，表明起源于中枢神经系统。我们对从von Hippel-Lindau病患者中获得的小脑组织进行了结构和地形分析，以识别和表征中枢神经系统中发育停滞的结构元件。我们检查了5例无肿瘤的von Hippel-Lindau病患者和3例非von Hippel-Lindau病对照的整个小脑。在所有的，9小脑发育停滞的结构元件检测和地形图在385块冯希佩尔-林道病小脑。在214块对照小脑中没有发现发育停滞的结构元件。发育停滞的结构元件由表达缺氧诱导因子（HIF）2α但不表达HIF 1 α或brachyury的低分化细胞组成，并优先涉及小脑背的分子层。我们第一次确定和表征了von Hippel-Lindau患者中枢神经系统中发育停滞的结构元件。我们提供的证据表明，发育停滞的结构元素在小脑是由发育停滞的成血管细胞祖细胞在小脑背的分子层。
There is increasing evidence that suggests that knockout of tumor-suppressor gene function causes developmental arrest and protraction of cellular differentiation. In the peripheral nervous system of patients with the tumor-suppressor gene disorder, von Hippel–Lindau disease, we have demonstrated developmentally arrested structural elements composed of hemangioblast progenitor cells. Some developmentally arrested structural elements progress to a frank tumor, hemangioblastoma. However, in von Hippel–Lindau disease, hemangioblastomas are frequently observed in the cerebellum, suggesting an origin in the central nervous system. We performed a structural and topographic analysis of cerebellar tissues obtained from von Hippel–Lindau disease patients to identify and characterize developmentally arrested structural elements in the central nervous system. We examined the entire cerebella of five tumor-free von Hippel–Lindau disease patients and of three non-von Hippel–Lindau disease controls. In all, 9 cerebellar developmentally arrested structural elements were detected and topographically mapped in 385 blocks of von Hippel–Lindau disease cerebella. No developmentally arrested structural elements were seen in 214 blocks from control cerebella. Developmentally arrested structural elements are composed of poorly differentiated cells that express hypoxia-inducible factor (HIF)2α, but not HIF1α or brachyury, and preferentially involve the molecular layer of the dorsum cerebelli. For the first time, we identify and characterize developmentally arrested structural elements in the central nervous system of von Hippel–Lindau patients. We provide evidence that developmentally arrested structural elements in the cerebellum are composed of developmentally arrested hemangioblast progenitor cells in the molecular layer of the dorsum cerebelli.
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DOI：
10.1073/pnas.93.20.10595
发表时间：
1996-10-01
影响因子：
11.1
作者：
Iliopoulos, O;Levy, AP;Goldberg, MA
通讯作者：
Goldberg, MA
影响因子：
11.2
作者：
Gläsker, S;Lonser, RR;Vortmeyer, AO
通讯作者：
Vortmeyer, AO
影响因子：
4.8
作者：
Cockman, ME;Masson, N;Maxwell, PH
通讯作者：
Maxwell, PH
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
DOI：
10.1038/ejhg.2008.162
发表时间：
2008-11
期刊：
European journal of human genetics : EJHG
影响因子：
--
作者：
Blumenthal GM;Dennis PA
通讯作者：
Dennis PA