Journal Article

DKFZ-2024-01209

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cancer-specific epigenome identifies oncogenic hijacking by nuclear factor I family proteins for medulloblastoma progression.

Shiraishi, R. ; Cancila, G. ; Kumegawa, K. ; Torrejon, J. ; Basili, I. ; Bernardi, F. ; Silva, P. B. G. d.DKFZ* ; Wang, W. ; Chapman, O. ; Yang, L. ; Jami, M. ; Nishitani, K. ; Arai, Y. ; Xiao, Z. ; Yu, H. ; Lo Re, V. ; Marsaud, V. ; Talbot, J. ; Lombard, B. ; Loew, D. ; Jingu, M. ; Okonechnikov, K.DKFZ* ; Sone, M. ; Motohashi, N. ; Aoki, Y. ; Pfister, S. M.DKFZ* ; Chavez, L. ; Hoshino, M. ; Maruyama, R. ; Ayrault, O. ; Kawauchi, D.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.devcel.2024.05.013

Abstract: Normal cells coordinate proliferation and differentiation by precise tuning of gene expression based on the dynamic shifts of the epigenome throughout the developmental timeline. Although non-mutational epigenetic reprogramming is an emerging hallmark of cancer, the epigenomic shifts that occur during the transition from normal to malignant cells remain elusive. Here, we capture the epigenomic changes that occur during tumorigenesis in a prototypic embryonal brain tumor, medulloblastoma. By comparing the epigenomes of the different stages of transforming cells in mice, we identify nuclear factor I family of transcription factors, known to be cell fate determinants in development, as oncogenic regulators in the epigenomes of precancerous and cancerous cells. Furthermore, genetic and pharmacological inhibition of NFIB validated a crucial role of this transcription factor by disrupting the cancer epigenome in medulloblastoma. Thus, this study exemplifies how epigenomic changes contribute to tumorigenesis via non-mutational mechanisms involving developmental transcription factors.

Keyword(s): brain tumor ; cerebellar granule cell ; cerebellum ; epigenome ; medulloblastoma ; mouse model ; nuclear factor I

Note: 2024 Sep 9;59(17):2302-2319.e12

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)

Research Program(s):

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

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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