Molecular and morphologic correlates of the alternative lengthening of telomeres phenotype in high-grade astrocytomas

Doreen N Nguyen, Christopher M Heaphy, Roeland F de Wilde, Brent A Orr, Yazmin Odia, Charles G Eberhart, Alan K Meeker, Fausto J Rodriguez*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

61 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)237-243
Number of pages7
JournalBrain Pathology
Volume23
Issue number3
DOIs
Publication statusPublished - May 2013
Externally publishedYes

Bibliographical note

© 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

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