Second hit deletion size in von Hippel-Lindau disease

Sven Gläsker, Tae Sung Sohn, Hiroaki Okamoto, Jie Li, Russell R. Lonser, Edward H. Oldfield, Alexander Vortmeyer, Zhengping Zhuang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

von Hippel-Lindau (VHL) disease is caused by germline mutations of the VHL tumor suppressor gene. Affected individuals are predisposed to development of multiple neoplastic and preneoplastic lesions of different organs. A "second hit," which is usually represented by deletion in the wild-type VHL allele at 3p25, is necessary for initiation of tumor formation. The impact of the size of this deletion is thought to be critical, because other tumor suppressor genes are located nearby, but this has not yet been studied in detail. We mapped the deletion size of the "second hit" in microdissected tissue from 16 different VHL-associated lesions from the same patient using 10 polymorphic chromosome 3 markers. We found that the deletion size is highly variable, ranging from short deletions around the VHL gene to complete loss of the chromosome 3. The deletion sizes are not correlated with the site of the germline mutation, the affected organ, or the type or biological behavior of the tumor. Even preneoplastic cystic structures may harbor entire loss of the chromosome 3, suggesting that loss of VHL gene function alone is not immediately causative for neoplastic growth, but further events, either mutations and deletions in other chromosomes or epigenetic or other than genetic phenomena, are required for tumor formation.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalAnnals of Neurology
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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von Hippel-Lindau Disease
Chromosomes, Human, Pair 3
Germ-Line Mutation
Tumor Suppressor Genes
Genetic Phenomena
Neoplasms
Sequence Deletion
Genetic Markers
Epigenomics
Genes
Chromosomes
Alleles
Growth

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Gläsker, S., Sohn, T. S., Okamoto, H., Li, J., Lonser, R. R., Oldfield, E. H., ... Zhuang, Z. (2006). Second hit deletion size in von Hippel-Lindau disease. Annals of Neurology, 59(1), 105-110. https://doi.org/10.1002/ana.20704

Second hit deletion size in von Hippel-Lindau disease. / Gläsker, Sven; Sohn, Tae Sung; Okamoto, Hiroaki; Li, Jie; Lonser, Russell R.; Oldfield, Edward H.; Vortmeyer, Alexander; Zhuang, Zhengping.

In: Annals of Neurology, Vol. 59, No. 1, 01.01.2006, p. 105-110.

Research output: Contribution to journalArticle

Gläsker, S, Sohn, TS, Okamoto, H, Li, J, Lonser, RR, Oldfield, EH, Vortmeyer, A & Zhuang, Z 2006, 'Second hit deletion size in von Hippel-Lindau disease', Annals of Neurology, vol. 59, no. 1, pp. 105-110. https://doi.org/10.1002/ana.20704
Gläsker S, Sohn TS, Okamoto H, Li J, Lonser RR, Oldfield EH et al. Second hit deletion size in von Hippel-Lindau disease. Annals of Neurology. 2006 Jan 1;59(1):105-110. https://doi.org/10.1002/ana.20704
Gläsker, Sven ; Sohn, Tae Sung ; Okamoto, Hiroaki ; Li, Jie ; Lonser, Russell R. ; Oldfield, Edward H. ; Vortmeyer, Alexander ; Zhuang, Zhengping. / Second hit deletion size in von Hippel-Lindau disease. In: Annals of Neurology. 2006 ; Vol. 59, No. 1. pp. 105-110.
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