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Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas.
- Source :
-
Cancer research [Cancer Res] 1998 Feb 01; Vol. 58 (3), pp. 504-8. - Publication Year :
- 1998
-
Abstract
- 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.
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Cell Transformation, Neoplastic genetics
Cerebellar Neoplasms pathology
DNA, Neoplasm genetics
Female
Hemangioblastoma pathology
Humans
Loss of Heterozygosity
Male
Middle Aged
Stromal Cells chemistry
Stromal Cells pathology
Von Hippel-Lindau Tumor Suppressor Protein
Cerebellar Neoplasms genetics
Genes, Tumor Suppressor
Hemangioblastoma genetics
Ligases
Proteins genetics
Tumor Suppressor Proteins
Ubiquitin-Protein Ligases
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 58
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 9458097