Mapping pediatric brain tumors to their origins in the developing cerebellum.

Autor:	Okonechnikov K; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Joshi P; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Developmental Origins of Pediatric Cancer Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sepp M; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Leiss K; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Sarropoulos I; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Murat F; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.; INRAE, LPGP, Rennes, France., Sill M, Beck P; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Chan KC; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Korshunov A; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Sah F; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Deng MY; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sturm D; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany., DeSisto J; Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA., Donson AM; Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA., Foreman NK; Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA.; Children's Hospital Colorado, Aurora, CO, USA., Green AL; Morgan Adams Foundation Pediatric Brain Tumor Research Program, University of Colorado School of Medicine, Aurora, CO, USA.; Children's Hospital Colorado, Aurora, CO, USA., Robinson G; Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, USA., Orr BA; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA., Gao Q; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN, USA.; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA., Darrow E; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA., Hadley JL; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA., Northcott PA; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA., Gojo J; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics and Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria.; Department of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow, Russia., Kawauchi D; Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, NCNP, Tokyo, Japan., Hovestadt V; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, USA.; Broad Institute of Harvard and MIT, Cambridge, USA., Filbin MG; Department of Pediatric Oncology, Dana-Farber Boston Children's Cancer and Blood Disorders Center, Boston, USA.; Broad Institute of Harvard and MIT, Cambridge, USA., von Deimling A; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany., Zuckermann M; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Pajtler KW; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Kool M; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, the Netherlands., Jones DTW; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Jäger N; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany., Kutscher LM; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Developmental Origins of Pediatric Cancer Junior Research Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Kaessmann H; Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany., Pfister SM; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2023 Oct 03; Vol. 25 (10), pp. 1895-1909.
DOI:	10.1093/neuonc/noad124
Abstrakt:	Background: Distinguishing the cellular origins of childhood brain tumors is key for understanding tumor initiation and identifying lineage-restricted, tumor-specific therapeutic targets. Previous strategies to map the cell-of-origin typically involved comparing human tumors to murine embryonal tissues, which is potentially limited due to species-specific differences. The aim of this study was to unravel the cellular origins of the 3 most common pediatric brain tumors, ependymoma, pilocytic astrocytoma, and medulloblastoma, using a developing human cerebellar atlas. Methods: We used a single-nucleus atlas of the normal developing human cerebellum consisting of 176 645 cells as a reference for an in-depth comparison to 4416 bulk and single-cell transcriptome tumor datasets, using gene set variation analysis, correlation, and single-cell matching techniques. Results: We find that the astroglial cerebellar lineage is potentially the origin for posterior fossa ependymomas. We propose that infratentorial pilocytic astrocytomas originate from the oligodendrocyte lineage and MHC II genes are specifically enriched in these tumors. We confirm that SHH and Group 3/4 medulloblastomas originate from the granule cell and unipolar brush cell lineages. Radiation-induced gliomas stem from cerebellar glial lineages and demonstrate distinct origins from the primary medulloblastoma. We identify tumor genes that are expressed in the cerebellar lineage of origin, and genes that are tumor specific; both gene sets represent promising therapeutic targets for future study. Conclusion: Based on our results, individual cells within a tumor may resemble different cell types along a restricted developmental lineage. Therefore, we suggest that tumors can arise from multiple cellular states along the cerebellar "lineage of origin." (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
Databáze:	MEDLINE
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