Journal Article

DKFZ-2026-00538

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies.

Gudenas, B. L. ; Ahmad, S. T. ; Englinger, B. ; Liu, A. P. Y. ; Zhao, M. ; Paul, L. ; Hadley, J. ; Li, Y. ; Batts, M. ; Mittal, P. ; Wu, S. C. ; Lewis, S. A. ; Han, K. ; Soliman, T. ; Lin, H. ; Janke, L. ; Meredith, D. ; Pfaff, E.DKFZ* ; Gojo, J. ; Cotter, J. ; Klimo, P. ; Boop, F. A. ; Gajjar, A. ; Robinson, G. W. ; Rosén, G. ; Alexandrescu, S. ; Jones, D. T. W.DKFZ* ; Orr, B. A. ; Swartling, F. J. ; Filbin, M. G. ; Northcott, P. A.

2026
Cell Press Cambridge, Mass.

Abstract: 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.

Keyword(s): central nervous system cancers ; developmental origins ; genetic dependencies ; genetically engineered mouse models ; medulloblastoma ; photoreceptor ; pineal gland ; pineoblastoma ; retinoblastoma ; single-cell genomics

Note: #DKTKZFB26# / epub

---

Contributing Institute(s):

1. Pädiatrische Gliomforschung (B360)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---