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A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal...

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Autori principali: Gudenas, Brian (Autore) , Ahmad, Shiekh Tanveer (Autore) , Englinger, Bernhard (Autore) , Liu, Anthony P. Y. (Autore) , Zhao, Miao (Autore) , Paul, Leena (Autore) , Hadley, Jennifer (Autore) , Li, Yiran (Autore) , Batts, Melissa (Autore) , Mittal, Priya (Autore) , Wu, Stephanie C. (Autore) , Lewis, Sara A. (Autore) , Han, Katie (Autore) , Soliman, Taha (Autore) , Lin, Hong (Autore) , Janke, Laure (Autore) , Meredith, David (Autore) , Pfaff, Elke (Autore) , Gojo, Johannes (Autore) , Cotter, Jennifer (Autore) , Klimo, Paul (Autore) , Boop, Frederick A. (Autore) , Gajjar, Amar (Autore) , Robinson, Giles W. (Autore) , Rosén, Gabriela (Autore) , Alexandrescu, Sanda (Autore) , Jones, David T. W. (Autore) , Orr, Brent A. (Autore) , Swartling, Fredrik J. (Autore) , Filbin, Mariella G. (Autore) , Northcott, Paul A. (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 13 April 2026
In: Cancer cell
Year: 2026, Volume: 44, Fascicolo: 4, Pages: 831-845.e10
ISSN:1878-3686
DOI:10.1016/j.ccell.2026.02.010
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ccell.2026.02.010
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S153561082600108X
Testo
Note sull'autore:Brian L. Gudenas, Shiekh Tanveer Ahmad, Bernhard Englinger, Anthony P.Y. Liu, Miao Zhao, Leena Paul, Jennifer Hadley, Yiran Li, Melissa Batts, Priya Mittal, Stephanie C. Wu, Sara A. Lewis, Katie Han, Taha Soliman, Hong Lin, Laure Janke, David Meredith, Elke Pfaff, Johannes Gojo, Jennifer Cotter, Paul Klimo, Frederick A. Boop, Amar Gajjar, Giles W. Robinson, Gabriela Rosén, Sanda Alexandrescu, David T.W. Jones, Brent A. Orr, Fredrik J. Swartling, Mariella G. Filbin, and Paul A. Northcott
Descrizione
Riassunto:Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with developmental counterparts to retrace cellular origins. Integrative computational analyses map pineoblastoma origins to transient, cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncover a tumor-associated photoreceptor signature (TAPS) common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.
Descrizione del documento:Online verfügbar: 5. März 2026, Artikelversion: 13. April 2026
Gesehen am 16.06.2026
Descrizione fisica:Online Resource
ISSN:1878-3686
DOI:10.1016/j.ccell.2026.02.010

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