PMID- 28040793
OWN - NLM
STAT- MEDLINE
DCOM- 20170623
LR  - 20170717
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 76
IP  - 1
DP  - 2017 Jan 1
TI  - 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.
PG  - 61-66
LID - 10.1093/jnen/nlw106 [doi]
AB  - 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.
CI  - (c) 2017 American Association of Neuropathologists, Inc. All rights reserved.
FAU - Brugger, Fabienne
AU  - Brugger F
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
FAU - Dettmer, Matthias S
AU  - Dettmer MS
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
FAU - Neuenschwander, Maja
AU  - Neuenschwander M
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
FAU - Perren, Aurel
AU  - Perren A
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
FAU - Marinoni, Ilaria
AU  - Marinoni I
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
FAU - Hewer, Ekkehard
AU  - Hewer E
AD  - Institute of Pathology, University of Bern, Bern, Switzerland.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Child
MH  - Child, Preschool
MH  - *Disease Progression
MH  - Ependymoma/diagnosis/*genetics
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - *Phenotype
MH  - Promoter Regions, Genetic/genetics
MH  - Telomerase/*genetics
MH  - Telomere/genetics
MH  - Telomere Homeostasis/*genetics
MH  - Young Adult
OTO - NOTNLM
OT  - ATRX
OT  - Alternative lengthening of telomeres
OT  - DAXX
OT  - Ependymoma
OT  - Ependymosarcoma
OT  - TERT
EDAT- 2017/01/04 06:00
MHDA- 2017/06/24 06:00
CRDT- 2017/01/02 06:00
PHST- 2017/01/04 06:00 [pubmed]
PHST- 2017/06/24 06:00 [medline]
PHST- 2017/01/02 06:00 [entrez]
AID - nlw106 [pii]
AID - 10.1093/jnen/nlw106 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2017 Jan 1;76(1):61-66. doi: 10.1093/jnen/nlw106.