Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry.

Autor:	Petrilli LL; Department of Onco-hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital- IRCCS, Rome, Italy., Fuoco C; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Palma A; Department of Onco-hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital- IRCCS, Rome, Italy., Pasquini L; Core Facilities, Istituto Superiore di Sanità, Rome, Italy., Pericoli G; Department of Onco-hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital- IRCCS, Rome, Italy., Grabovska Y; Division of Molecular Pathology, Institute of Cancer Research, Sutton, United Kingdom., Mackay A; Division of Molecular Pathology, Institute of Cancer Research, Sutton, United Kingdom., Rossi S; Department of Laboratories-Pathology Unit, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy., Carcaboso AM; Pediatric Hematology and Oncology, Hospital Sant Joan de Deu, Institut de Recerca Sant Joan de Deu, Barcelona, Spain., Carai A; Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children's Hospital -IRCCS, Rome, Italy., Mastronuzzi A; Neuro-oncology Unit, Department of Onco-haematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy., Jones C; Division of Molecular Pathology, Institute of Cancer Research, Sutton, United Kingdom., Cesareni G; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy., Locatelli F; Department of Onco-hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital- IRCCS, Rome, Italy., Vinci M; Department of Onco-hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital- IRCCS, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Dec 08; Vol. 12, pp. 1016343. Date of Electronic Publication: 2022 Dec 08 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.1016343
Abstrakt:	Paediatric-type diffuse high-grade gliomas (PDHGG) are aggressive tumors affecting children and young adults, with no effective treatment. These highly heterogeneous malignancies arise in different sites of the Central Nervous System (CNS), carrying distinctive molecular alterations and clinical outcomes (inter-tumor heterogeneity). Moreover, deep cellular and molecular profiling studies highlighted the coexistence of genetically and phenotypically different subpopulations within the same tumor mass (intra-tumor heterogeneity). Despite the recent advances made in the field, the marked heterogeneity of PDHGGs still impedes the development of effective targeted therapies and the identification of suitable biomarkers. In order to fill the existing gap, we used mass cytometry to dissect PDHGG inter- and intra-heterogeneity. This is one of the most advanced technologies of the "-omics" era that, using antibodies conjugated to heavy metals, allows the simultaneous measurement of more than 40 markers at single-cell level. To this end, we analyzed eight PDHGG patient-derived cell lines from different locational and molecular subgroups. By using a panel of 15 antibodies, directly conjugated to metals or specifically customized to detect important histone variants, significant differences were highlighted in the expression of the considered antigens. The single-cell multiparametric approach realized has deepened our understanding of PDHGG, confirming a high degree of intra- and inter-tumoral heterogeneity and identifying some antigens that could represent useful biomarkers for the specific PDHGG locational or molecular subgroups. 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 © 2022 Petrilli, Fuoco, Palma, Pasquini, Pericoli, Grabovska, Mackay, Rossi, Carcaboso, Carai, Mastronuzzi, Jones, Cesareni, Locatelli and Vinci.)
Databáze:	MEDLINE
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