Frontiers in Oncology (Oct 2024)
Impaired neutrophil-mediated cell death drives Ewing’s Sarcoma in the background of Down syndrome
- Serena Peirone,
- Serena Peirone,
- Elisa Tirtei,
- Elisa Tirtei,
- Anna Campello,
- Caterina Parlato,
- Caterina Parlato,
- Simonetta Guarrera,
- Simonetta Guarrera,
- Katia Mareschi,
- Katia Mareschi,
- Elena Marini,
- Elena Marini,
- Sebastian Dorin Asaftei,
- Luca Bertero,
- Mauro Papotti,
- Francesca Priante,
- Francesca Priante,
- Sarah Perrone,
- Sarah Perrone,
- Matteo Cereda,
- Matteo Cereda,
- Franca Fagioli,
- Franca Fagioli
Affiliations
- Serena Peirone
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
- Serena Peirone
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Elisa Tirtei
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Elisa Tirtei
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
- Anna Campello
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Caterina Parlato
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Caterina Parlato
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
- Simonetta Guarrera
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Simonetta Guarrera
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
- Katia Mareschi
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Katia Mareschi
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
- Elena Marini
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Elena Marini
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
- Sebastian Dorin Asaftei
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Luca Bertero
- Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
- Mauro Papotti
- Pathology Unit, Department of Oncology, University of Turin, Turin, Italy
- Francesca Priante
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Francesca Priante
- Department of Oncology, University of Torino, Candiolo, Italy
- Sarah Perrone
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Sarah Perrone
- Department of Oncology, University of Torino, Candiolo, Italy
- Matteo Cereda
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
- Matteo Cereda
- Italian Institute for Genomic Medicine, c/o IRCCS, Candiolo, Italy
- Franca Fagioli
- Paediatric Oncology Department, Regina Margherita Children’s Hospital, Turin, Italy
- Franca Fagioli
- Department of Public Health and Paediatrics, University of Turin, Turin, Italy
- DOI
- https://doi.org/10.3389/fonc.2024.1429833
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
