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Peer-reviewedCC BY-NC-ND 4.0Cancer Genomics & Proteomics

Route-aware Therapeutic Target Atlas for Desmoplastic Small Round Cell Tumor

  • COREY GOLDMAN1,2
  1. 1Medalliance Medical Health Services, Bronx, NY, U.S.A.
  2. 2NYU Langone Health, New York, NY, U.S.A.
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Abstract

Background/Aim: Desmoplastic small round cell tumor (DSRCT) is an EWSR1::WT1-driven sarcoma with limited disease-specific options. We assembled an 80-gene candidate-and-control panel and evaluated bulk tumor RNA prevalence, cellular source, fusion-associated expression change, normal-tissue expression, and treatment-specific validation requirements to construct a DSRCT target atlas.

Materials and Methods: The panel was examined in two bulk RNA-sequencing cohorts comprising 61 patients and 86 tumor specimens. Technical libraries were collapsed to specimens and specimens to patients on each cohort’s native counts per million (CPM) or transcripts per million (TPM) scale; threshold and collapse-rule sensitivity analyses were performed. Exploratory supporting data comprised single-cell RNA sequencing (two distinct specimens analyzed separately, 9,520 cells total; both sharing one anonymized patient label), spatial transcriptomics (five patients, six specimens), three fusion-suppression cohorts, one cell-state cohort, and Human Protein Atlas (HPA)/Genotype-Tissue Expression (GTEx) normal-tissue references.

Results: CD276, CD200, ERBB2, ALCAM, IGF2, TFRC, and the established diagnostic marker CACNA2D2 were detected in 61/61 patients. CLDN6 was detected in 33/61 patients [54%; Wilson 95% confidence interval (CI)=42-66%] and SSTR3 in 59/61 (97%; 95% CI=89-99%). CACNA2D2, FGFR4, and MSLN expression decreased after EWSR1::WT1 suppression in all three cohorts, whereas results for several other candidates differed among cohorts.

Conclusion: The atlas identifies the next validation study required for each target; RNA detection alone does not establish protein abundance, therapeutic accessibility, efficacy, or safety.

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Cite

BibTeXRIS
BibTeX
@article{goldman2026routeaware,
  title = {{Route-aware Therapeutic Target Atlas for Desmoplastic Small Round Cell Tumor}},
  author = {COREY GOLDMAN},
  journal = {Cancer Genomics \& Proteomics},
  year = {2026},
  month = oct,
  doi = {10.21873/cgp.20617},
  url = {https://doi.org/10.21873/cgp.20617},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Route-aware Therapeutic Target Atlas for Desmoplastic Small Round Cell Tumor
AU  - COREY GOLDMAN
PY  - 2026
DA  - 2026/10/31
JO  - Cancer Genomics & Proteomics
DO  - 10.21873/cgp.20617
UR  - https://doi.org/10.21873/cgp.20617
AB  - Background/Aim: Desmoplastic small round cell tumor (DSRCT) is an EWSR1::WT1-driven sarcoma with limited disease-specific options. We assembled an 80-gene candidate-and-control panel and evaluated bulk tumor RNA prevalence, cellular source, fusion-associated expression change, normal-tissue expression, and treatment-specific validation requirements to construct a DSRCT target atlas.  Materials and Methods: The panel was examined in two bulk RNA-sequencing cohorts comprising 61 patients and 86 tumor specimens. Technical libraries were collapsed to specimens and specimens to patients on each cohort’s native counts per million (CPM) or transcripts per million (TPM) scale; threshold and collapse-rule sensitivity analyses were performed. Exploratory supporting data comprised single-cell RNA sequencing (two distinct specimens analyzed separately, 9,520 cells total; both sharing one anonymized patient label), spatial transcriptomics (five patients, six specimens), three fusion-suppression cohorts, one cell-state cohort, and Human Protein Atlas (HPA)/Genotype-Tissue Expression (GTEx) normal-tissue references.  Results: CD276, CD200, ERBB2, ALCAM, IGF2, TFRC, and the established diagnostic marker CACNA2D2 were detected in 61/61 patients. CLDN6 was detected in 33/61 patients [54%; Wilson 95% confidence interval (CI)=42-66%] and SSTR3 in 59/61 (97%; 95% CI=89-99%). CACNA2D2, FGFR4, and MSLN expression decreased after EWSR1::WT1 suppression in all three cohorts, whereas results for several other candidates differed among cohorts.  Conclusion: The atlas identifies the next validation study required for each target; RNA detection alone does not establish protein abundance, therapeutic accessibility, efficacy, or safety.
SN  - 1109-6535
SN  - 1790-6245
ER  -