Journal Article

DKFZ-2021-01432

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Notch1 switches progenitor competence in inducing medulloblastoma.

Ballabio, C. ; Gianesello, M. ; Lago, C. ; Okonechnikov, K.DKFZ* ; Anderle, M. ; Aiello, G. ; Antonica, F. ; Zhang, T. ; Gianno, F. ; Giangaspero, F. ; Hassan, B. A. ; Pfister, S.DKFZ* ; Tiberi, L.

2021
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.abd2781

Abstract: The identity of the cell of origin is a key determinant of cancer subtype, progression, and prognosis. Group 3 medulloblastoma (MB) is a malignant childhood brain cancer with poor prognosis and few candidates as putative cell of origin. We overexpressed the group 3 MB genetic drivers MYC and Gfi1 in different candidate cells of origin in the postnatal mouse cerebellum. We found that S100b+ cells are competent to initiate group 3 MB, and we observed that S100b+ cells have higher levels of Notch1 pathway activity compared to Math1+ cells. We found that additional activation of Notch1 in Math1+ and Sox2+ cells was sufficient to induce group 3 MB upon MYC/Gfi1 expression. Together, our data suggest that the Notch1 pathway plays a critical role in group 3 MB initiation.

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. DKTK HD zentral (HD01)

Research Program(s):

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

Appears in the scientific report 2021

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