Nguyen, Doreen N.;
Heaphy, Christopher M.;
de Wilde, Roeland F.;
Orr, Brent A.;
Odia, Yazmin;
Eberhart, Charles G.;
Meeker, Alan K.;
Rodriguez, Fausto J.
Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High‐Grade Astrocytomas
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Medientyp:
E-Artikel
Titel:
Molecular and Morphologic Correlates of the Alternative Lengthening of Telomeres Phenotype in High‐Grade Astrocytomas
Beteiligte:
Nguyen, Doreen N.;
Heaphy, Christopher M.;
de Wilde, Roeland F.;
Orr, Brent A.;
Odia, Yazmin;
Eberhart, Charles G.;
Meeker, Alan K.;
Rodriguez, Fausto J.
Erschienen:
Wiley, 2013
Erschienen in:
Brain Pathology, 23 (2013) 3, Seite 237-243
Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Recent studies suggest that the telomere maintenance mechanism known as alternative lengthening of telomeres (<jats:styled-content style="fixed-case">ALT</jats:styled-content>) is relatively more common in specific glioma subsets and strongly associated with <jats:italic><jats:styled-content style="fixed-case">ATRX</jats:styled-content></jats:italic> mutations. We retrospectively examined 116 high‐grade astrocytomas (32 pediatric glioblastomas, 65 adult glioblastomas, 19 anaplastic astrocytomas) with known <jats:styled-content style="fixed-case">ALT</jats:styled-content> status using tissue microarrays to identify associations with molecular and phenotypic features. Immunohistochemistry was performed using antibodies against <jats:styled-content style="fixed-case">ATRX</jats:styled-content>, <jats:styled-content style="fixed-case">DAXX</jats:styled-content>, p53 and <jats:styled-content style="fixed-case">IDH1<jats:sup>R132H</jats:sup></jats:styled-content> mutant protein. <jats:italic><jats:styled-content style="fixed-case">EGFR</jats:styled-content></jats:italic> amplification was evaluated by fluorescence <jats:italic>in situ</jats:italic> hybridization (<jats:styled-content style="fixed-case">FISH</jats:styled-content>). Almost half of fibrillary and gemistocytic astrocytomas (44%) demonstrated <jats:styled-content style="fixed-case">ALT</jats:styled-content>. Conversely all gliosarcomas (n = 4), epithelioid (n = 2), giant cell (n = 2) and adult small cell astrocytomas (n = 7) were <jats:styled-content style="fixed-case">ALT</jats:styled-content> negative. The <jats:styled-content style="fixed-case">ALT</jats:styled-content> phenotype was positively correlated with the presence of round cells (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.002), microcysts (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> < 0.0002), <jats:styled-content style="fixed-case">IDH1</jats:styled-content> mutant protein (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> < 0.0001), <jats:styled-content style="fixed-case">ATRX</jats:styled-content> protein loss (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> < 0.0001), strong P53 immunostaining (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> < 0.0001) and absence of <jats:italic><jats:styled-content style="fixed-case">EGFR</jats:styled-content></jats:italic> amplification (<jats:italic><jats:styled-content style="fixed-case">P</jats:styled-content></jats:italic> = 0.004). There was no significant correlation with <jats:styled-content style="fixed-case">DAXX</jats:styled-content> expression. We conclude that <jats:styled-content style="fixed-case">ALT</jats:styled-content> 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 <jats:styled-content style="fixed-case">ALT</jats:styled-content> in high‐grade astrocytomas.</jats:p>