Single cell RNA-sequencing of Ewing sarcoma tumors demonstrates transcriptional heterogeneity and clonal evolution.
Goodspeed, A.; Bodlak, A.; Nelson-Taylor, S.; Oike, N.; Shirai, R.; Walker, D.; Porfilio, T. E.; Treece, A.; Black, J. O.; Donaldson, N.; Cost, C.; Garrington, T.; Greffe, B.; Luna-Fineman, S.; Demedis, J.; Lake, J. A.; Danis, E.; Verneris, M. R.; Hayashi, M.
Show abstract
Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.
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