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Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Sporadic hemangioblastomas are characterized by cryptic VHL inactivation

Authors :
Shankar, Ganesh Mani
Taylor-Weiner, Amaro
Lelic, Nina
Jones, Robert T
Kim, James C
Francis, Joshua M
Abedalthagafi, Malak S
Borges, Lawrence Francis
Coumans, Jean-Valery C E
Curry, William Thomas
Nahed, Brian Vala
Shin, John H
Paek, Sun Ha
Park, Sung-Hye
Stewart, Chip
Lawrence, Michael S
Cibulskis, Kristian
Thorner, Aaron R
Van Hummelen, Paul
Stemmer-Rachamimov, Anat
Batchelor, Tracy Todd
Carter, Scott Lambert
Hoang, Mai P
Santagata, Sandro
Louis, David N.
Barker, Frederick George
Meyerson, Matthew Langer
Getz, Gad A
Brastianos, Priscilla Kalliope
Cahill, Daniel P.
Source :
Shankar, Ganesh M, Amaro Taylor-Weiner, Nina Lelic, Robert T Jones, James C Kim, Joshua M Francis, Malak Abedalthagafi, et al. 2014. Sporadic Hemangioblastomas Are Characterized by Cryptic VHL Inactivation. Acta Neuropathol Commun 2, no. 1. doi:10.1186/s40478-014-0167-x.
Publication Year :
2014
Publisher :
Springer Nature, 2014.

Abstract

Hemangioblastomas consist of 10-20% neoplastic “stromal” cells within a vascular tumor cell mass of reactive pericytes, endothelium and lymphocytes. Familial cases of central nervous system hemangioblastoma uniformly result from mutations in the Von Hippel-Lindau (VHL) gene. In contrast, inactivation of VHL has been previously observed in only a minority of sporadic hemangioblastomas, suggesting an alternative genetic etiology. We performed deep-coverage DNA sequencing on 32 sporadic hemangioblastomas (whole exome discovery cohort n = 10, validation n = 22), followed by analysis of clonality, copy number alteration, and somatic mutation. We identified somatic mutation, loss of heterozygosity and/or deletion of VHL in 8 of 10 discovery cohort tumors. VHL inactivating events were ultimately detected in 78% (25/32) of cases. No other gene was significantly mutated. Overall, deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of these tumors at higher frequencies than previously reported. Our findings support the central role of VHL inactivation in the molecular pathogenesis of both familial and sporadic hemangioblastomas.

Details

Language :
English
ISSN :
20515960
Database :
Digital Access to Scholarship at Harvard (DASH)
Journal :
Shankar, Ganesh M, Amaro Taylor-Weiner, Nina Lelic, Robert T Jones, James C Kim, Joshua M Francis, Malak Abedalthagafi, et al. 2014. Sporadic Hemangioblastomas Are Characterized by Cryptic VHL Inactivation. Acta Neuropathol Commun 2, no. 1. doi:10.1186/s40478-014-0167-x.
Publication Type :
Academic Journal
Accession number :
edshld.1.36880596
Document Type :
Journal Article
Full Text :
https://doi.org/10.1186/s40478-014-0167-x