ArticleThe Journal of pathology2025
The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma.
Article in The Journal of pathology, 2025. 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.
- Sacral benign notochordal cell tumor with atypical imaging features and 16-year spontaneous partial regression: A case report.Radiology case reports · 2026Article
- ATF4-mediated stress response as a therapeutic vulnerability in chordoma.Molecular oncology · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
The aim of this research was to investigate the pathogenesis of the bone cancer chordoma and the role of the germline rs2305089 SNP in TBXT. Using medical imaging and genotyping studies, we observed that benign notochordal cell tumours (BNCTs) were associated with chordomas and with the variant rs2305089 A-allele with enrichment of the AA genotype compared to controls. We engineered in vitro mesoderm models, representing notochord, which showed higher expression of TBXT and activation of its regulatory network in the presence of the variant A allele. Heterozygotes (GA) displayed enrichment of Wnt/β-catenin and epithelial mesenchymal transition pathways, faster cell migratory capacity, and altered expression of endoplasmic reticulum and intracellular transport mediators. WT lines (GG) were enriched for metabolic pathways and MTORC1 signalling, suggesting that rs2305089 genotype regulates notochord vacuoles during notochord regression. By leveraging patient-derived data and functional studies, we show that the variant rs2305089 A-allele predisposes to BNCTs and ultimately to chordomas. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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