First Generation Tools for the Modeling of Capicua-Family Fusion Oncoprotein-Driven Cancers (February 2025 Dataset)

The rearrangement of separate genes into neomorphic fusion oncogenes can occur after chromosomal damage and repair, causing cancer. In the case of sarcomas, several tumor types are driven by fusion oncogenes comprised of various partner genes. We study fusions involving capicua (CIC), a developmental transcriptional repressor whose fusion to 3' partner genes including DUX4, NUTM1, and LEUTX drives devastating tumors of the soft tissue, central nervous system, and spine. Here we develop the first tools to investigate previously understudied fusions of CIC and ATXN1 and express them in 293T cells to uncover convergent/divergent biology between various CIC-family fusions depending on what the specific partner genes are. polyA-selected bulk RNAseq of 293T cells transfected with empty vector, HA-ATXN1::DUX4, or HA-ATXN1::DUX4 delAXH expressing constructs, 48 hours post transfection.