Supplementary Data for Route-Aware Immunotherapy Target Atlas for Desmoplastic Small Round Cell Tumor
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Background/Aim: Desmoplastic small round cell tumor (DSRCT) is an aggressive EWSR1::WT1-driven sarcoma with few disease-specific therapeutic options. We sought to evaluate and route nominated immunotherapy targets while separating tumor prevalence from modality-specific therapeutic usability. Materials and Methods: An iteratively assembled 80-gene candidate-and-control panel—an initial 60-gene manifest followed by a 20-gene literature-driven clinical-actionability add-on—was assessed across 61 open-access patient bulk RNA-sequencing profiles, patient single-cell and spatial transcriptomes, fusion-perturbation and cell-state models, and Human Protein Atlas/GTEx normal-tissue resources. Targets were assigned to surface-payload, theranostic, pathway, glycan, or peptide-HLA routes using auditable evidence domains. Results: Six therapeutic candidates—CD276, ERBB2, ALCAM, CD200, IGF2, and TFRC—were detected in all 61 tumors; CACNA2D2 was also universal but was retained as a diagnostic benchmark. Malignant-compartment and fusion-program filters removed bulk-expression false positives. CLDN6 combined subgroup prevalence (34/61) with restricted normal-tissue expression, whereas SSTR3 showed near-universal prevalence (59/61) and defined an imaging-led theranostic hypothesis. ERBB2, CD276, MSLN, and related surface candidates remained route-conditioned because of normal-organ liabilities. Conclusion: The curated panel demonstrates multiple recurrently expressed candidate targets, each requiring route-specific interpretation according to cellular distribution, normal-organ liability, and therapeutic accessibility. Translational prioritization should pair each target with protein-level, functional, and safety validation appropriate to its therapeutic modality rather than rank targets by RNA prevalence alone.



