PMID- 22928601
OWN - NLM
STAT- MEDLINE
DCOM- 20131028
LR  - 20231212
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 23
IP  - 3
DP  - 2013 May
TI  - Molecular and morphologic correlates of the alternative lengthening of telomeres 
      phenotype in high-grade astrocytomas.
PG  - 237-43
LID - 10.1111/j.1750-3639.2012.00630.x [doi]
AB  - Recent studies suggest that the telomere maintenance mechanism known as 
      alternative lengthening of telomeres (ALT) is relatively more common in specific 
      glioma subsets and strongly associated with ATRX mutations. We retrospectively 
      examined 116 high-grade astrocytomas (32 pediatric glioblastomas, 65 adult 
      glioblastomas, 19 anaplastic astrocytomas) with known ALT status using tissue 
      microarrays to identify associations with molecular and phenotypic features. 
      Immunohistochemistry was performed using antibodies against ATRX, DAXX, p53 and 
      IDH1(R132H) mutant protein. EGFR amplification was evaluated by fluorescence in 
      situ hybridization (FISH). Almost half of fibrillary and gemistocytic 
      astrocytomas (44%) demonstrated ALT. Conversely all gliosarcomas (n = 4), 
      epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) 
      were ALT negative. The ALT phenotype was positively correlated with the presence 
      of round cells (P = 0.002), microcysts (P < 0.0002), IDH1 mutant protein 
      (P < 0.0001), ATRX protein loss (P < 0.0001), strong P53 immunostaining 
      (P < 0.0001) and absence of EGFR amplification (P = 0.004). There was no 
      significant correlation with DAXX expression. We conclude that ALT represents a 
      specific phenotype in high-grade astrocytomas with distinctive pathologic and 
      molecular features. Future studies are required to clarify the clinical and 
      biological significance of ALT in high-grade astrocytomas.
CI  - (c) 2012 The Authors; Brain Pathology (c) 2012 International Society of 
      Neuropathology.
FAU - Nguyen, Doreen N
AU  - Nguyen DN
AD  - Department of Pathology, The Johns Hopkins University School of Medicine, 
      Baltimore, MD, USA.
FAU - Heaphy, Christopher M
AU  - Heaphy CM
FAU - de Wilde, Roeland F
AU  - de Wilde RF
FAU - Orr, Brent A
AU  - Orr BA
FAU - Odia, Yazmin
AU  - Odia Y
FAU - Eberhart, Charles G
AU  - Eberhart CG
FAU - Meeker, Alan K
AU  - Meeker AK
FAU - Rodriguez, Fausto J
AU  - Rodriguez FJ
LA  - eng
GR  - P30 CA006973/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120924
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Co-Repressor Proteins)
RN  - 0 (DAXX protein, human)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Nuclear Proteins)
RN  - EC 3.6.4.- (DNA Helicases)
RN  - EC 3.6.4.12 (ATRX protein, human)
RN  - EC 3.6.4.12 (X-linked Nuclear Protein)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Astrocytoma/*pathology/ultrastructure
MH  - Brain Neoplasms/*pathology/ultrastructure
MH  - Child
MH  - Child, Preschool
MH  - Co-Repressor Proteins
MH  - DNA Helicases/metabolism
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Microarray Analysis
MH  - Middle Aged
MH  - Molecular Chaperones
MH  - Nuclear Proteins/metabolism
MH  - Phenotype
MH  - Survival Analysis
MH  - Telomere/*pathology/ultrastructure
MH  - X-linked Nuclear Protein
MH  - Young Adult
PMC - PMC3827727
MID - NIHMS448285
EDAT- 2012/08/30 06:00
MHDA- 2013/10/29 06:00
PMCR- 2012/09/24
CRDT- 2012/08/30 06:00
PHST- 2012/07/10 00:00 [received]
PHST- 2012/08/16 00:00 [accepted]
PHST- 2012/08/30 06:00 [entrez]
PHST- 2012/08/30 06:00 [pubmed]
PHST- 2013/10/29 06:00 [medline]
PHST- 2012/09/24 00:00 [pmc-release]
AID - BPA630 [pii]
AID - 10.1111/j.1750-3639.2012.00630.x [doi]
PST - ppublish
SO  - Brain Pathol. 2013 May;23(3):237-43. doi: 10.1111/j.1750-3639.2012.00630.x. Epub 
      2012 Sep 24.