Journal Article

DKFZ-2026-02375

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency.

Tao, R. ; Erkek-Ozhan, S. (First author)DKFZ* ; Xu, B. ; Matsui, Y. ; Mittal, P. ; Smith, K. S. ; Li, Y. ; Filipovic, D. ; Xu, R. ; Gao, Q. ; Darrow, E. ; Kumar, R. ; Djekidel, N. ; Bajpai, R. ; Hadley, J. ; Batts, M. ; Lewis, S. A. ; Soliman, T. ; Reilly, C. ; Bhanu, N. V. ; Paul, L. ; Lin, H. ; Gudenas, B. ; Lowe, K. ; Zapatka, M.DKFZ* ; Sieber, L.DKFZ* ; Jones, D.DKFZ* ; Kool, M.DKFZ* ; Waszak, S. M. ; Hovestadt, V.DKFZ* ; Buchhalter, I.DKFZ* ; Ryzhova, M. ; Korshunov, A.DKFZ* ; Lichter, P.DKFZ* ; Chavez, L. ; Kutscher, L.DKFZ* ; Garcia, B. A. ; Pruett-Miller, S. M. ; Zhou, X. ; Orr, B. A. ; Robinson, G. W. ; Wu, G. ; Korbel, J.DKFZ* ; Peng, J. C. ; Pfister, S. (Last author)DKFZ* ; Northcott, P. A.

2026
Macmillan Publishers Limited, part of Springer Nature London

Abstract: Medulloblastoma is a biologically heterogeneous childhood cerebellar tumor harboring frequent chromatin-modifying gene alterations. How these alterations promote transcriptional programs governing malignancy remains poorly defined. To address this knowledge gap, we evaluated chromatin states across medulloblastoma subgroups by multi-modal integration of histone modifications with mutational, DNA methylation and transcriptomic profiles. A bivalent/poised enhancer (EnhBiv) state was specifically enriched at the promoters of neurodevelopmental genes in Group 3/4 medulloblastoma. Integrative bioinformatics coupled with chromatin occupancy studies identified aberrant KDM2B binding at EnhBiv-enriched promoters. CRISPR-mediated knockout or acute protein degradation of KDM2B selectively suppressed the growth of medulloblastoma models in vitro and in vivo. Mechanistically, KDM2B promotes sequential recruitment of Polycomb repressive complexes (PRC1/PRC2) and EnhBiv chromatin, thereby repressing neuronal differentiation programs. Collectively, we provide foundational insights into an epigenetic basis of medulloblastoma, nominating KDM2B as a selective dependency in high-risk subgroups that warrants consideration as a candidate therapeutic target.

Note: #EA:B062#LA:B062# / #DKTKZFB26# / #NCTZFB26# / epub

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Contributing Institute(s):

1. Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)
3. Molekulare Genetik (B060)
4. Entwicklungsbiolog. Ursprünge pädiatrischer Krebserkrankungen (B430)
5. Pädiatrische Gliomforschung (B360)
6. W610 Core Facility Omics IT (W610)
7. KKE Neuropathologie (B300)
8. Mechanismen der genetischen Variation und Datenwissenschaft (B480)
9. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

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

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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