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Claudin-6 Protein Expression in Atypical Teratoid/Rhabdoid Tumors Is Strongly Enriched in the Molecular Subgroup
Victoria E Fincke1,2, Christian Thomas3, Michael C Frühwald1,2
1Pediatrics and Adolescent Medicine, Swabian Children's Cancer Center, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
Abstract:
Claudin-6 has emerged as a promising immunotherapeutic target, yet protein-level data in atypical teratoid/rhabdoid tumors (AT/RTs) have been inconsistent. We analyzed 36 well-characterized AT/RT samples and found membranous claudin-6 protein expression in 58% of cases, with striking enrichment in the molecular subgroup AT/RT-TYR (100%) and significantly higher staining scores compared with AT/RT-SHH and AT/RT-MYC. Correspondingly, AT/RT-TYR showed lower CLDN6 promoter methylation. Pilot spatial transcriptomic experiments in AT/RT-TYR confirmed heterogeneous CLDN6 transcription, and co-expression analyses linked CLDN6 to epithelial-mesenchymal transition-related genes. These findings clarify subgroup-specific expression patterns and support claudin-6 as a biologically and therapeutically relevant target in AT/RT-TYR.
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