Unraveling the Biology

Unraveling the Biology of Desmoplastic Small Round Cell Tumor

DSRCT is suspected to be an AR-driven tumor

DSRCT Timeline

1991 DSRCT described by Gerald and Rosai

1994 EWS-WT1 fusion reported by Ladanyi and Gerald

2007 Fine et al. tested androgen blockade on six patients

2018 Bulbul et al. showed AR enrichment by IHC in 35 cases

AR drives DSRCT proliferation and growth AR binds to shared motifs with PCa Lamhamedi-Cherradi, Salah-Eddine, et al. "The androgen receptor is a therapeutic target in desmoplastic small round cell sarcoma." Nature Communications 13.1 (2022): 1-16.

Disease progression model of Prostate cancer

Does DSRCT resemble PCa biology, where a loss of AR could lead to a NE phenotype?

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Unraveling the Biology of Desmoplastic Small Round Cell Tumor

Generation of a DSRCT single-nucleus Atlas Collection of 13 fresh-frozen specimens - representative of 9 patients Identified DSRCT from stromal cells • EWS-WT1 Score from EWS-WT1 target genes • CNV Score from inferCNV Can we identify AR and NE phenotypes by transcriptomic signatures?

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Unraveling the Biology of Desmoplastic Small Round Cell Tumor

An AR and a separate NE phenotype exists in DSRCT

Wide variation in AR and NE signatures AR and NE are inversely related Two DSRCT phenotypes –AR and NE

NE+

AR+

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