ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2013
The alternative lengthening of telomere phenotype is significantly associated with loss of ATRX expression in high-grade pediatric and adult astrocytomas: a multi-institutional study of 214 astrocytomas.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Systematic review and meta-analysis of genomic alterations in acral melanoma.Pigment cell & melanoma research · 2022Pooled it
- Current and emerging therapies in IDH-mutant glioma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Isocitrate Dehydrogenase-Mutant Astrocytomas: Risk Stratification and Therapeutic Advance.MedComm · 2026Review
- Review
- M2 macrophage infiltration associated with CXCL8 predicts grade 4 prognosis and differentiates glioma grades.Discover oncology · 2025Article
- Functional analysis of telomere maintenance mechanisms is more informative than immunohistochemistry for ATRX mutation interpretation in Gliomas.Acta neuropathologica communications · 2025Article
- Precision radiotherapy with molecular-profiling of CNS tumours.Journal of neuro-oncology · 2025Review
- The Role of Mutant IDH Inhibitors in the Treatment of Glioma.Current neurology and neuroscience reports · 2024Review
- IDH inhibition in gliomas: from preclinical models to clinical trials.Nature reviews. Neurology · 2024Review
- DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks.Nucleic acids research · 2024Article
- Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma.Clinical and translational medicine · 2024Review
- Effects of p53 and ATRX inhibition on telomeric recombination in aging fibroblasts.Frontiers in oncology · 2024Article
- Article
- ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors.Cancers · 2022Article
- Applications of Artificial Intelligence Based on Medical Imaging in Glioma: Current State and Future Challenges.Frontiers in oncology · 2022Review
- Impact of Chromatin Dynamics and DNA Repair on Genomic Stability and Treatment Resistance in Pediatric High-Grade Gliomas.Cancers · 2021Review
- Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism.International journal of molecular sciences · 2021Article
- SMARCAL1 loss and alternative lengthening of telomeres (ALT) are enriched in giant cell glioblastoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Glioma-Specific Diffusion Signature in Diffusion Kurtosis Imaging.Journal of clinical medicine · 2021Article
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Loss-of-function of alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein leads to a phenotype called alternative lengthening of telomeres (ALT) in some tumors. High-grade astrocytomas comprise a heterogeneous group of central nervous system tumors. We examined a large cohort of adult (91) and pediatric (n=88) high-grade astrocytomas as well as lower grade forms (n=35) for immunohistochemical loss of ATRX protein expression and the presence of ALT using telomere-specific fluorescence in situ hybridization, with further correlation to other known genetic alterations. We found that in pediatric high-grade astrocytomas, 29.6% of tumors were positive for ALT and 24.5% were immunonegative for the ATRX protein, these two alterations being highly associated with one another (P<0.0001). In adult high-grade astrocytomas, 26.4% of tumors were similarly positive for ALT, including 80% of ATRX protein immunonegative cases (P<0.0001). Similar frequencies were found in 11 adult low-grade astrocytomas, whereas all 24 pilocytic astrocytomas were negative for ALT. We did not find any significant correlations between isocitrate dehydrogenase status and either ALT positivity or ATRX protein expression in our adult high-grade astrocytomas. In both cohorts, however, the ALT positive high-grade astrocytomas showed more frequent amplification of the platelet-derived growth factor receptor alpha gene (PDGFRA; 45% and 50%, respectively) than the ALT negative counterparts (18% and 26%; P=0.03 for each). In summary, our data show that the ALT and ATRX protein alterations are common in both pediatric and adult high-grade astrocytomas, often with associated PDGFRA gene amplification.
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