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Impaired neutrophil-mediated cell death drives Ewing's Sarcoma in a two years old child with Down Syndrome

Peirone, S.; Tirtei, E.; Campello, A.; Parlato, C.; Guarrera, S.; Mareschi, K.; Marini, E.; Asaftei, S. D.; Bertero, L.; Papotti, M.; Cereda, M.; Fagioli, F.

2023-05-31 oncology
10.1101/2023.05.30.23289664 medRxiv
Show abstract

Ewings Sarcoma (EWS) has been reported in seven children with Down Syndrome (DS). To date, a detailed assessment of this solid tumor in DS patients is still missing. Here, we characterized a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches. The tumor showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability. In this context, the tumor underwent nearly genome-wide haploidization resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered the fast evolution of this EWS.

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