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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