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

Autor:	Peirone S; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy., Tirtei E; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy.; Department of Public Health and Paediatrics, University of Turin, Turin, Italy., Campello A; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy., Parlato C; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy.; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Guarrera S; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy.; Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy., Mareschi K; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy.; Department of Public Health and Paediatrics, University of Turin, Turin, Italy., Marini E; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy.; Department of Public Health and Paediatrics, University of Turin, Turin, Italy., Asaftei SD; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy., Bertero L; Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy., Papotti M; Pathology Unit, Department of Oncology, University of Turin, Turin, Italy., Priante F; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy.; Department of Oncology, University of Torino, Candiolo, Italy., Perrone S; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy.; Department of Oncology, University of Torino, Candiolo, Italy., Cereda M; Department of Biosciences, Università degli Studi di Milano, Milan, Italy.; Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy., Fagioli F; Paediatric Oncology Department, Regina Margherita Children's Hospital, Turin, Italy.; Department of Public Health and Paediatrics, University of Turin, Turin, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Oct 03; Vol. 14, pp. 1429833. Date of Electronic Publication: 2024 Oct 03 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1429833
Abstrakt:	Introduction: Ewing 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. Methods: Here, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches. Results: The 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. Discussion: In 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Peirone, Tirtei, Campello, Parlato, Guarrera, Mareschi, Marini, Asaftei, Bertero, Papotti, Priante, Perrone, Cereda and Fagioli.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu