Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High‐Grade Astrocytomas. (24th September 2012)

• Record Type: Journal Article
• Authors: Nguyen, Doreen N.; Heaphy, Christopher M.; de, Roeland F.; Orr, Brent A.; Odia, Yazmin; Eberhart, Charles G.; Meeker, Alan K.; Rodriguez, Fausto J.
• Is Part Of: Brain pathology. Volume 23:Number 3(2013:May)
• Page Start: 237
• Page End: 243
• Publication Date: 2012-09-24
• Subjects: Nervous system -- Diseases -- Periodicals; Brain -- Diseases -- Periodicals; Neurology -- Periodicals; Brain Diseases -- Periodicals; Cerveau -- Maladies -- Périodiques; Système nerveux -- Maladies -- Périodiques; Neurologie -- Périodiques; 616.805
• DOI: 10.1111/j.1750-3639.2012.00630.x
• Languages: English
• ISSNs: 1015-6305

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>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 <italic>ATRX</italic> 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<sup>R132H</sup> mutant protein. <italic>EGFR</italic> amplification was evaluated by fluorescence <italic>in situ</italic> 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 (<italic>P</italic> = 0.002), microcysts (<italic>P</italic> < 0.0002), IDH1 mutant protein (<italic>P</italic> < 0.0001), ATRX protein loss (<italic>P</italic> < 0.0001), strong P53 immunostaining (<italic>P</italic> < 0.0001) and absence of <italic>EGFR</italic> amplification (<italic>P</italic> = 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.</p> </abstract>