Ewing’s 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.
Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in a two years old child with Down Syndrome / S. Peirone, E. Tirtei, A. Campello, C. Parlato, S. Guarrera, K. Mareschi, E. Marini, S. Dorin Asaftei, L. Bertero, M. Papotti, F. Priante, S. Perrone, M. Cereda, F. Fagioli. - (2023 Aug 28).
Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in a two years old child with Down Syndrome
S. PeironeCo-primo
;M. Cereda
Co-ultimo
;
2023
Abstract
Ewing’s 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.File | Dimensione | Formato | |
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