Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in the background of Down syndrome

Autor: Serena Peirone, Elisa Tirtei, Anna Campello, Caterina Parlato, Simonetta Guarrera, Katia Mareschi, Elena Marini, Sebastian Dorin Asaftei, Luca Bertero, Mauro Papotti, Francesca Priante, Sarah Perrone, Matteo Cereda, Franca Fagioli
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Oncology, Vol 14 (2024)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2024.1429833
Popis: IntroductionEwing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made.MethodsHere, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches.ResultsThe tumour 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.DiscussionIn this context, the tumour underwent genome-wide near haploidisation resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered rapid evolution of this EWS.
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