: Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.

Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas

De Bacco, Francesca;Orzan, Francesca;Crisafulli, Giovanni;Prelli, Marta;Isella, Claudio;Albano, Raffaella;Reato, Gigliola;Erriquez, Jessica;D'Ambrosio, Antonio;Zeppa, Pietro;Altieri, Roberto;Cassoni, Paola;Garbossa, Diego;Cassisa, Anna;Bartolini, Alice;Comoglio, Paolo M;Boccaccio, Carla
2023-01-01

Abstract

: Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.
2023
42
8
1
30
CP: Cancer; GBM-PNC; cancer stem cell; gene amplification; gene mutation; glioblastoma; glioblastoma stem-like cell; growth factor; receptor tyrosine kinase; tumor heterogeneity
De Bacco, Francesca; Orzan, Francesca; Crisafulli, Giovanni; Prelli, Marta; Isella, Claudio; Casanova, Elena; Albano, Raffaella; Reato, Gigliola; Erriquez, Jessica; D'Ambrosio, Antonio; Panero, Mara; Dall'Aglio, Carmine; Casorzo, Laura; Cominelli, Manuela; Pagani, Francesca; Melcarne, Antonio; Zeppa, Pietro; Altieri, Roberto; Morra, Isabella; Cassoni, Paola; Garbossa, Diego; Cassisa, Anna; Bartolini, Alice; Pellegatta, Serena; Comoglio, Paolo M; Finocchiaro, Gaetano; Poliani, Pietro L; Boccaccio, Carla
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1925670
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