TY  - JOUR
AU  - Ballabio, Claudio
AU  - Gianesello, Matteo
AU  - Lago, Chiara
AU  - Okonechnikov, Konstantin
AU  - Anderle, Marica
AU  - Aiello, Giuseppe
AU  - Antonica, Francesco
AU  - Zhang, Tingting
AU  - Gianno, Francesca
AU  - Giangaspero, Felice
AU  - Hassan, Bassem A
AU  - Pfister, Stefan
AU  - Tiberi, Luca
TI  - Notch1 switches progenitor competence in inducing medulloblastoma.
JO  - Science advances
VL  - 7
IS  - 26
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DKFZ-2021-01432
SP  - eabd2781 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34162555
DO  - DOI:10.1126/sciadv.abd2781
UR  - https://inrepo02.dkfz.de/record/169352
ER  -