ArticlePLoS genetics2019
Loss of atrx cooperates with p53-deficiency to promote the development of sarcomas and other malignancies.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- ATR-X syndrome: genetics, clinical spectrum, and management.Human genetics · 2021Pooled it
- MiT fusions, TSC1-TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa.Nature communications · 2026Article
- ATRX safeguards cellular identity duringbioRxiv : the preprint server for biology · 2026Article
- ATRX: From Chromatin Remodeling to Disease.Genesis (New York, N.Y. : 2000) · 2025Review
- Transcriptional patterns of cancer-related genes in primary and metastatic tumours revealed by machine learning.BMC biology · 2025Article
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.Genome medicine · 2024Article
- Sirtuin 2 inhibition modulates chromatin landscapes genome-wide to induce senescence in ATRX-deficient malignant glioma.Neuro-oncology · 2024Article
- Mutant ATRX: pathogenesis of ATRX syndrome and cancer.Frontiers in molecular biosciences · 2024Review
- Therapeutically targeting the unique disease landscape of pediatric high-grade gliomas.Frontiers in oncology · 2024Review
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- Distinct dosage compensations of ploidy-sensitive and -insensitive X chromosome genes during development and in diseases.iScience · 2023Article
- Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes.BMC cancer · 2023Article
- Alternative Lengthening of Telomeres in Cancer Confers a Vulnerability to Reactivation of p53 Function.Cancer research · 2022Article
- Zebrafish Models of Paediatric Brain Tumours.International journal of molecular sciences · 2022Review
- What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine.Cancers · 2022Review
- Review
- Modeling Brain Tumors: A Perspective Overview ofFrontiers in molecular neuroscience · 2022Review
- Undifferentiated pleomorphic sarcoma of the lateral thigh with KRAS/NF1 co-mutation recurred after repetitive surgical resection: A case report and review of the literature.Frontiers in surgery · 2022Article
- Comparison of the oncogenomic landscape of canine and feline hemangiosarcoma shows novel parallels with human angiosarcoma.Disease models & mechanisms · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SWI/SNF-family chromatin remodeling protein ATRX is a tumor suppressor in sarcomas, gliomas and other malignancies. Its loss of function facilitates the alternative lengthening of telomeres (ALT) pathway in tumor cells, while it also affects Polycomb repressive complex 2 (PRC2) silencing of its target genes. To further define the role of inactivating ATRX mutations in carcinogenesis, we knocked out atrx in our previously reported p53/nf1-deficient zebrafish line that develops malignant peripheral nerve sheath tumors and gliomas. Complete inactivation of atrx using CRISPR/Cas9 was lethal in developing fish and resulted in an alpha-thalassemia-like phenotype including reduced alpha-globin expression. In p53/nf1-deficient zebrafish neither peripheral nerve sheath tumors nor gliomas showed accelerated onset in atrx+/- fish, but these fish developed various tumors that were not observed in their atrx+/+ siblings, including epithelioid sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma and rare types of carcinoma. These cancer types are included in the AACR Genie database of human tumors associated with mutant ATRX, indicating that our zebrafish model reliably mimics a role for ATRX-loss in the early pathogenesis of these human cancer types. RNA-seq of p53/nf1- and p53/nf1/atrx-deficient tumors revealed that down-regulation of telomerase accompanied ALT-mediated lengthening of the telomeres in atrx-mutant samples. Moreover, inactivating mutations in atrx disturbed PRC2-target gene silencing, indicating a connection between ATRX loss and PRC2 dysfunction in cancer development.
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