ArticlePLoS genetics2012
Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 406 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
406 citing papers in PubMed, 1 synthesis or guideline pooled it, 630 citations in OpenAlex.
- Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis.Frontiers in endocrinology · 2021Pooled it
- Alternative lengthening of telomeres in small well-differentiated pancreatic neuroendocrine tumors: independent validation and cross-platform concordance.Virchows Archiv : an international journal of pathology · 2026Article
- Clustered structural variant hotspots enable oncogenic addiction and plasticity in osteosarcoma.bioRxiv : the preprint server for biology · 2026Article
- Article
- Twisting the End Game: How Telomere Chromatin Modifications Shape Telomere Maintenance.Aging cell · 2026Review
- Telomere-driven replicative crisis is driven by large-scale changes in genomic architecture.Genome research · 2026Article
- SMARCAL1 is a candidate therapeutic target for ALT-positive tumors.Genes & development · 2026Article
- Selective killing of ALT-cancer cells by Withaferin-A involves destabilization of Rad51 and disruption of DNA repair.Cell death & disease · 2026Article
- Structure and mechanism of inhibition of lysine demethylase 2A (KDM2A) by compound 183c.Communications chemistry · 2026Article
- ATRX inactivation disrupts global chromatin state and topology to dysregulate neurodevelopmental pathways in glioma pathogenesis.Nucleic acids research · 2026Article
- Complex structural variations functionally inactivate the telomerase chaperone TCAB1 in osteosarcoma.BMC cancer · 2026Article
- Multi-omic profiles of neuroendocrine neoplasms of the pancreas: an integrated landscape.Molecular cancer · 2026Review
- Orphan nuclear receptors recruit TRIM28 to promote telomeric H3K9me3 for the ALT pathway.The EMBO journal · 2026Article
- Chromosome-arm-specific telomere length governs dual modes of structural genome evolution in IDH-mutant astrocytoma.bioRxiv : the preprint server for biology · 2026Article
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- Review
- The ATRXt Protein Represses rDNA Transcription While Mirroring ATRX Interactions and Heterochromatin Localization.International journal of molecular sciences · 2026Article
- Local heterochromatin enrichment promotes telomere clustering and PML nuclear body assembly at telomeres.Cell reports · 2026Article
- Telomere Crisis Shapes Cancer Evolution.Cold Spring Harbor perspectives in biology · 2026Review
- SFPQ directs histone H3.3 deposition to R-loops in DNA repeats to protect genome stability.Nature communications · 2026Article
346 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 9 institutions in 2 countries.
Funding
Abstract
The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent pathway for telomere maintenance that is active in a significant subset of human cancers and in vitro immortalized cell lines. ALT is thought to involve templated extension of telomeres through homologous recombination, but the genetic or epigenetic changes that unleash ALT are not known. Recently, mutations in the ATRX/DAXX chromatin remodeling complex and histone H3.3 were found to correlate with features of ALT in pancreatic neuroendocrine cancers, pediatric glioblastomas, and other tumors of the central nervous system, suggesting that these mutations might contribute to the activation of the ALT pathway in these cancers. We have taken a comprehensive approach to deciphering ALT by applying genomic, molecular biological, and cell biological approaches to a panel of 22 ALT cell lines, including cell lines derived in vitro. Here we show that loss of ATRX protein and mutations in the ATRX gene are hallmarks of ALT-immortalized cell lines. In addition, ALT is associated with extensive genome rearrangements, marked micronucleation, defects in the G2/M checkpoint, and altered double-strand break (DSB) repair. These attributes will facilitate the diagnosis and treatment of ALT positive human cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.