Project description:The object of this study is to identify the molecular signature underlying the therapeutic potential of N3-induced growth arrest in Desmoplastic Small Round Cell Tumor (DSRCT). The molecular hallmark of DSRCT is the EWS-WT1 fusion protein formed by chromosomal translocations found in DSRCT. The N-terminal transactivation domain of EWS is fused to the C-terminal DNA binding domain of WT1, creating an oncogenic transcription factor. We have recently discovered that addition of N3 supplement to growing DSRCT cells leads to a rapid cessation of cell growth.
Project description:Desmoplastic small round cell tumor (DSRCT) is a rare pediatric cancer caused by the EWSR1-WT1 fusion oncogene. Despite initial response to chemotherapy, DSRCT has a recurrence rate of over 80% leading to poor patient prognosis with a 5-year survival rate of only 15-25%. Owing to the rarity of DSRCT, sample scarcity is a barrier to understanding DSRCT biology and developing effective therapies. Here, we performed RNA-sequencing on a novel pair of primary and recurrent DSRCT tumors harvested from the same patient 5-years apart. To gain insights into gene expression alterations associated with recurrence, we performed pathway analysis on Gene Ontology Biological Processes and KEGG pathways. Upregulated pathways in the recurrent tumor included DNA repair and mRNA splicing related pathways, while downregulated pathways included immune system function and focal adhesion. We further examined the expression of previously identified EWSR1-WT1 regulated targets, a large number of which were enriched in the recurrent tumor. Overall, this study provides novel understanding of DSRCT biology and a new RNA-seq data set to advance future studies.