ATRX loss predicts poor outcomes and reveals a therapeutic vulnerability to TEAD inhibition in soft tissue sarcomas -- CUT&RUN v2

Loss of ATRX is associated with aggressive tumor behavior, but the transcriptional regulatory mechanisms underlying ATRX-deficient sarcomas remain incompletely understood. In this study, we investigated chromatin and transcription factor regulatory changes associated with ATRX loss in sarcoma models.

Our analyses identified chromatin de-repression following ATRX loss and enrichment of transcription factor motifs, including PRDM4 and NFIX. To characterize the genomic regulatory programs associated with these transcription factors, we performed CUT&RUN profiling to map transcription factor occupancy in sarcoma cells. These data provide genome-wide profiles of transcription factor binding and support investigation of the regulatory mechanisms associated with ATRX loss in sarcoma.