ArticleNature communications2020
MYCN amplification and ATRX mutations are incompatible in neuroblastoma.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 124 citations in OpenAlex.
- Frequency and Clinical Significance of Clonal and Subclonal Driver Mutations in High-Risk Neuroblastoma at Diagnosis: A Children's Oncology Group Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Trial
- A functional landscape for chromosome 17q in neuroblastoma: balancing replication stress and genomic stability.British journal of cancer · 2026Review
- Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study.JCO precision oncology · 2026Article
- Review
- Telomere maintenance mechanisms are activated in ganglioneuroblastoma and ganglioneuroma.Oncology letters · 2026Article
- SMARCAL1 is a targetable synthetic lethal therapeutic vulnerability in ATRX-deficient gliomas that use alternative lengthening of telomeres.Neuro-oncology · 2026Article
- Article
- ATRX large deletions and truncating mutations are associated with primary induction chemotherapy resistance in high-risk neuroblastoma: a multicenter propensity-weighted cohort study.Frontiers in oncology · 2026Article
- The chromatin guardian ATRX is a strong prognostic biomarker in melanoma.Scientific reports · 2025Article
- ATRX: From Chromatin Remodeling to Disease.Genesis (New York, N.Y. : 2000) · 2025Review
- Silencing of SOD1 sensitises ATRX-deficient cells to camptothecin treatment through increased activity of the alternative lengthening of telomeres pathway.Human molecular genetics · 2025Article
- Association of TRDMT1 Gene Polymorphisms With Neuroblastoma Susceptibility: Insights From a Case-Control Study.Journal of cellular and molecular medicine · 2025Article
- Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- DNA methylation profiling for molecular classification of neuroblastoma.Clinical epigenetics · 2025Article
- Targeting Pathways in Neuroblastoma: Advances in Treatment Strategies and Clinical Outcomes.International journal of molecular sciences · 2025Review
- The Involvement of CSRP1 in Neuroblastoma Differentiation and Apoptosis Impacting Tumor-Suppressive Therapeutic Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- ATRX mutations mediate an immunogenic phenotype and macrophage infiltration in neuroblastoma.Cancer letters · 2025Article
- Sustained cancer-relevant alternative RNA splicing events driven by PRMT5 in high-risk neuroblastoma.Molecular oncology · 2025Article
- Identification of biomarkers and mechanism exploration of ferroptosis related genes regulated by m6A in type 2 diabetes mellitus.Hereditas · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
37 authors at 7 institutions in 1 country.
Funding
Abstract
Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX-histone chaperone complex, and that induced by MYCN-mediated metabolic reprogramming, leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
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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.