UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Evolution of VHL tumourigenesis in nerve root tissue

Vortmeyer, AO; Tran, MGB; Zeng, W; Glasker, S; Riley, C; Tsokos, M; ... Oldfield, EH; + view all (2006) Evolution of VHL tumourigenesis in nerve root tissue. J PATHOL , 210 (3) 374 - 382. 10.1002/path.2062.

Full text not available from this repository.

Abstract

Haemangioblastomas are the key central nervous system manifestation of von Hippel-Lindau (VHL) disease, which is caused by germline mutation of the VHL gene. We have recently shown that 'tumour-free' spinal cord from patients with VHL disease contains microscopic, poorly differentiated cellular aggregates in nerve root tissue, which we descriptively designated 'mesenchymal tumourlets'. Here we have investigated spinal cord tissue affected by multiple tumours. We show that a small subset of mesenchymal tumourlets extends beyond the nerve root to form proliferative VHL-deficient mesenchyme and frank haemangioblastoma. We thus demonstrate that tumourlets present potential, but true precursor material for haemangioblastoma. We further show that intraradicular tumourlets consist of scattered VHL-deficient cells with activation of HIF-2 alpha and HIF-dependent target proteins including CAIX and VEGF, and are associated with an extensive angiogenic response. In contrast, activation of HIF-1 alpha was only observed in the later stages of tumour progression. In addition, ultrastructural examination reveals gradual transition from poorly differentiated VHL-deficient cells into vacuolated cells with a 'stromal' cell phenotype. The evolution of frank haemangioblastoma seems to involve multiple steps from a large pool of precursor lesions. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John

Type:Article
Title:Evolution of VHL tumourigenesis in nerve root tissue
DOI:10.1002/path.2062
Keywords:VHL disease, nerve root, haemangioblastoma, hypoxia-inducible factor, VEGF, ENDOTHELIAL GROWTH-FACTOR, HIPPEL-LINDAU-DISEASE, VASCULAR-PERMEABILITY FACTOR, TUMOR-SUPPRESSOR GENE, UP-REGULATION, HEMANGIOBLASTOMA, DEFICIENCY, EXPRESSION, BRAIN, CELLS
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

Archive Staff Only: edit this record