Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease

Sharon B. Shively, Eric A. Falke, Jie Li, Maxine G.B. Tran, Eli R. Thompson, Patrick H. Maxwell, Erich Roessler, Edward H. Oldfield, Russell R. Lonser, Alexander Vortmeyer

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1023-1030
Number of pages8
JournalModern Pathology
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

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Cerebellar Neoplasms
von Hippel-Lindau Disease
Cerebellum
Hemangioblasts
Hemangioblastoma
Central Nervous System
Tumor Suppressor Genes
Stem Cells
Cell Hypoxia
Peripheral Nervous System
Neoplasms

Keywords

  • hemangioblastoma
  • tumor precursors
  • von Hippel-Lindau disease

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Shively, S. B., Falke, E. A., Li, J., Tran, M. G. B., Thompson, E. R., Maxwell, P. H., ... Vortmeyer, A. (2011). Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease. Modern Pathology, 24(8), 1023-1030. https://doi.org/10.1038/modpathol.2011.61

Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease. / Shively, Sharon B.; Falke, Eric A.; Li, Jie; Tran, Maxine G.B.; Thompson, Eli R.; Maxwell, Patrick H.; Roessler, Erich; Oldfield, Edward H.; Lonser, Russell R.; Vortmeyer, Alexander.

In: Modern Pathology, Vol. 24, No. 8, 01.08.2011, p. 1023-1030.

Research output: Contribution to journalArticle

Shively, SB, Falke, EA, Li, J, Tran, MGB, Thompson, ER, Maxwell, PH, Roessler, E, Oldfield, EH, Lonser, RR & Vortmeyer, A 2011, 'Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease', Modern Pathology, vol. 24, no. 8, pp. 1023-1030. https://doi.org/10.1038/modpathol.2011.61
Shively SB, Falke EA, Li J, Tran MGB, Thompson ER, Maxwell PH et al. Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease. Modern Pathology. 2011 Aug 1;24(8):1023-1030. https://doi.org/10.1038/modpathol.2011.61
Shively, Sharon B. ; Falke, Eric A. ; Li, Jie ; Tran, Maxine G.B. ; Thompson, Eli R. ; Maxwell, Patrick H. ; Roessler, Erich ; Oldfield, Edward H. ; Lonser, Russell R. ; Vortmeyer, Alexander. / Developmentally arrested structures preceding cerebellar tumors in von Hippel-Lindau disease. In: Modern Pathology. 2011 ; Vol. 24, No. 8. pp. 1023-1030.
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