TERT Promoter Mutations but not the Alternative Lengthening of Telomeres Phenotype Are Present in a Subset of Ependymomas and Are Associated With Adult Onset and Progression to Ependymosarcoma.

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Serval ID
serval:BIB_D763C6DC25B1
Type
Article: article from journal or magazin.
Collection
Publications
Title
TERT Promoter Mutations but not the Alternative Lengthening of Telomeres Phenotype Are Present in a Subset of Ependymomas and Are Associated With Adult Onset and Progression to Ependymosarcoma.
Journal
Journal of neuropathology and experimental neurology
Author(s)
Brügger F., Dettmer M.S., Neuenschwander M., Perren A., Marinoni I., Hewer E.
ISSN
1554-6578 (Electronic)
ISSN-L
0022-3069
Publication state
Published
Issued date
01/01/2017
Peer-reviewed
Oui
Volume
76
Number
1
Pages
61-66
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Genetic signatures related to telomere maintenance have emerged as powerful classifiers among CNS tumors. These include the alternative lengthening of telomeres (ALT) phenotype associated with mutations in the ATRX and DAXX genes and recurrent point mutations in the TERT gene promoter. We investigated a patient cohort covering the entire spectrum of childhood and adult ependymomas (n = 128), including subependymomas and myxopapillary ependymomas, for the presence of TERT promoter mutations, for loss of ATRX or DAXX expression by immunohistochemistry (as surrogates as underlying gene mutations), and for the ALT phenotype by fluorescence in situ hybridization (FISH). TERT promoter mutations were identified in 9/120 (7%) of tumors, all of which were conventional ependymomas occurring in adults. TERT promoter mutations were associated with older age and intracranial localization. Remarkably, 2 of these tumors progressed to ependymosarcoma upon recurrence. No tumors displayed an ALT phenotype by FISH or were ATRX or DAXX deficient by immunohistochemistry. In sum, TERT promoter mutations are present in a subset of mostly intracranial conventional ependymomas in adults and may be relevant for the uncommon progression to ependymosarcoma. Loss of ATRX immunoreactivity is a useful marker to rule out ependymoma in specific diagnostic settings.
Keywords
Adolescent, Adult, Age of Onset, Aged, Child, Child, Preschool, Disease Progression, Ependymoma/diagnosis, Ependymoma/genetics, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Mutation/genetics, Phenotype, Promoter Regions, Genetic/genetics, Telomerase/genetics, Telomere/genetics, Telomere Homeostasis/genetics, Young Adult, ATRX, Alternative lengthening of telomeres, DAXX, Ependymoma, Ependymosarcoma, TERT
Pubmed
Web of science
Open Access
Yes
Create date
31/08/2020 12:02
Last modification date
10/11/2020 6:26
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