{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T16:27:59Z","timestamp":1775060879916,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,2,27]],"date-time":"2006-02-27T00:00:00Z","timestamp":1140998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>MYCN<\/jats:italic> amplification. The critical deleted region encompasses the locus of the von Hippel\u2010Lindau gene (<jats:italic>VHL<\/jats:italic>, 3p25). Constitutional loss of function mutations in the <jats:italic>VHL<\/jats:italic> 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 <jats:italic>VHL<\/jats:italic> 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 <jats:italic>VHL<\/jats:italic> in NB, we did mRNA expression analysis and sought evidence for <jats:italic>VHL<\/jats:italic> gene inactivation. Although no evidence for a classic tumor suppressor role for <jats:italic>VHL<\/jats:italic> in NB could be obtained, a strong correlation was observed between reduced levels of <jats:italic>VHL<\/jats:italic> mRNA and low patient survival probability (<jats:italic>p<\/jats:italic> = 0.013). Furthermore, <jats:italic>VHL<\/jats:italic> appears to have predictive power in <jats:italic>NTRK1<\/jats:italic> (<jats:italic>TRKA<\/jats:italic>) 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 <jats:italic>VHL<\/jats:italic> expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in <jats:italic>VHL<\/jats:italic> mRNA expression on protein stability of its downstream target hypoxia\u2010inducible factor \u03b1. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21888","type":"journal-article","created":{"date-parts":[[2006,2,27]],"date-time":"2006-02-27T21:47:54Z","timestamp":1141076874000},"page":"624-629","source":"Crossref","is-referenced-by-count":13,"title":["The von Hippel\u2010Lindau tumor suppressor gene expression level has prognostic value in 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