Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastoma

Hoebeeck, J ; Vandesompele, J ; Nilsson, Helén LU ; De Preter, K ; Van Roy, N ; De Smet, E ; Yigit, N ; De Paepe, A ; Laureys, G and Pahlman, S , et al. (2006) In International Journal of Cancer 119(3). p.624-629
Abstract
Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation... (More)
Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia-inducible factor alpha. (c) 2006 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
survival, neuroblastoma, 3p-deletion, VHL (von Hippel-Lindau), hypoxia
in
International Journal of Cancer
volume
119
issue
3
pages
624 - 629
publisher
John Wiley and Sons
external identifiers
  • wos:000238476800020
  • pmid:16506218
  • scopus:33745494694
ISSN
0020-7136
DOI
10.1002/ijc.21888
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)
id
8e71a6ca-be95-44d1-8398-ebe5a60836df (old id 406068)
date added to LUP
2016-04-01 11:52:05
date last changed
2021-01-06 04:06:32
@article{8e71a6ca-be95-44d1-8398-ebe5a60836df,
  abstract     = {Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia-inducible factor alpha. (c) 2006 Wiley-Liss, Inc.},
  author       = {Hoebeeck, J and Vandesompele, J and Nilsson, Helén and De Preter, K and Van Roy, N and De Smet, E and Yigit, N and De Paepe, A and Laureys, G and Pahlman, S and Speleman, F},
  issn         = {0020-7136},
  language     = {eng},
  number       = {3},
  pages        = {624--629},
  publisher    = {John Wiley and Sons},
  series       = {International Journal of Cancer},
  title        = {The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastoma},
  url          = {http://dx.doi.org/10.1002/ijc.21888},
  doi          = {10.1002/ijc.21888},
  volume       = {119},
  year         = {2006},
}