ArticleESMO rare cancers2026
ATRX loss in sarcomas is associated with dysregulated gene and transposable element expression, loss of DNA methylation, and worse survival.
Article in ESMO rare cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- Pleomorphism in Soft Tissue Sarcomas: Molecular Characteristics and Clinical Features.Medical sciences (Basel, Switzerland) · 2026Review
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4 authors.
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Abstract
Background: ATRX (α-thalassemia/mental retardation syndrome X-linked) is a tumor suppressor and key regulator of transcriptionally repressive epigenetic states. We investigate the impact of somatic Methods: Using data from The Cancer Genome Atlas (TCGA), we analyzed 234 tumors from patients with dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, soft tissue leiomyosarcoma (LMS), uterine LMS, and myxofibrosarcoma. Corresponding clinical outcome and patient data, DNA sequencing, RNA sequencing, and 450K methylation data were integrated to assess ATRX-dependent features. Results: ATRX loss was associated with significantly altered gene expression with the greatest impact in LMS/uterine LMS with reduction of expression of 31 (33%) genes and 63 (67%) genes up-regulated (false discovery rate <0.05), consistent with a role for ATRX in transcriptional silencing. Methylation profiling identified 269 differentially methylated CpGs (false discovery rate <0.05), with a marked hypomethylation effect (88% of CpGs) across all sarcomas. ATRX loss was associated with loss of TE silencing with 97% ( Conclusions: ATRX loss in sarcomas leads to DNA hypomethylation, increased expression of TEs, as well as transcriptional dysregulation affecting key oncogenic pathways. ATRX mutational status may serve as a potential biomarker for prognosis and therapeutic stratification. Future clinical trials investigating epigenetic therapies could offer novel treatment strategies for ATRX-deficient sarcomas.
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