Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease.
Mod Pathol
; 24(8): 1023-30, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21499240
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Cerebelo
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Enfermedad de von Hippel-Lindau
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mod Pathol
Asunto de la revista:
PATOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos