Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas

Jung Young Lee, Seung Myung Dong, Won Sang Park, Nam Jin Yoo, Choo Soung Kim, Ja Jun Jang, Je Geun Chi, Berton Zbar, Irina A. Lubensky, W. Marston Linehan, Alexander O. Vortmeyer, Zhengping Zhuang

Research output: Contribution to journalArticle

120 Scopus citations


Cerebellar hemangioblastoma is a benign central nervous system neoplasm with characteristic proliferation of vascular and stromal cells. There is increasing evidence that the stromal cell population may represent the neoplastic component of hemangioblastoma, whereas the vascular component may be composed of reactive, nonneoplastic cells. Therefore, successful genetic testing for loss of heterozygosity requires selective analysis of target cell populations. Here, tissue microdissection was used to selectively analyze the stromal cell component of 20 archival sporadic cerebellar hemangioblastomas for loss of heterozygosity at the Von-Hippel Lindau (VHL) gene and somatic VHL gene mutations. Allelic deletions at the VHL gene locus were detected in the stromal cell component with one or more markers (D3S1038, D3S1110, and/or 104/105) in 10 of 19 (52.6%) informative cases. In all cases, heterozygosity at the VHL gene locus was retained in the vascular component. In two cases, aberrant bands in exon 2 of the VHL gene were demonstrated in the stromal cells by PCR-based single-strand conformation polymorphism analysis, and somatic missense mutations were successfully characterized in two of the sporadic hemangioblastomas by direct sequencing. The results suggest that allelic losses and mutations of the VHL tumor suppressor gene play a role in sporadic cerebellar hemangioblastoma tumorigenesis. Furthermore, because the genetic changes were detected in selectively procured stromal cell areas, the data provide strong evidence that the stromal cell represents a neoplastic component of hemangioblastoma.

Original languageEnglish (US)
Pages (from-to)504-508
Number of pages5
JournalCancer Research
Issue number3
StatePublished - Feb 1 1998


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Lee, J. Y., Dong, S. M., Park, W. S., Yoo, N. J., Kim, C. S., Jang, J. J., Chi, J. G., Zbar, B., Lubensky, I. A., Linehan, W. M., Vortmeyer, A. O., & Zhuang, Z. (1998). Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas. Cancer Research, 58(3), 504-508.