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@ARTICLE{Hendrikse:181849,
author = {L. D. Hendrikse and P. Haldipur and O. Saulnier and J.
Millman and A. H. Sjoboen and A. W. Erickson and W. Ong and
V. Gordon and L. Coudière-Morrison and A. L. Mercier and M.
Shokouhian and R. A. Suárez and M. Ly and S. Borlase and D.
S. Scott and M. C. Vladoiu and H. Farooq and O. Sirbu and T.
Nakashima and S. Nambu and Y. Funakoshi and A. Bahcheli and
J. J. Diaz-Mejia and J. Golser and K. Bach and T. Phuong-Bao
and P. Skowron and E. Y. Wang and S. A. Kumar and P. Balin
and A. Visvanathan and J. J. Y. Lee and R. Ayoub and X. Chen
and X. Chen and K. L. Mungall and B. Luu and P. Bérubé and
Y. C. Wang and S. Pfister$^*$ and S.-K. Kim and O. Delattre
and F. Bourdeaut and F. Doz and J. Masliah-Planchon and W.
A. Grajkowska and J. Loukides and P. Dirks and M.
Fèvre-Montange and A. Jouvet and P. J. French and J. M.
Kros and K. Zitterbart and S. D. Bailey and C. G. Eberhart
and A. A. N. Rao and C. Giannini and J. M. Olson and M.
Garami and P. Hauser and J. J. Phillips and Y. S. Ra and C.
de Torres and J. Mora and K. K. W. Li and H.-K. Ng and W. S.
Poon and I. F. Pollack and E. López-Aguilar and G. Y.
Gillespie and T. E. Van Meter and T. Shofuda and R. Vibhakar
and R. C. Thompson and M. K. Cooper and J. B. Rubin and T.
Kumabe and S. Jung and B. Lach and A. Lolascon and V.
Ferrucci and P. de Antonellis and M. Zollo and G. Cinalli
and S. Robinson and D. S. Stearns and E. G. Van Meir and P.
Porrati and G. Finocchiaro and M. Massimino and C. G.
Carlotti and C. C. Faria and M. F. Roussel and F. Boop and
J. A. Chan and K. A. Aldinger and F. Razavi and E. Silvestri
and R. E. McLendon and E. M. Thompson and M. Ansari and M.
L. Garre and F. Chico and P. Eguía and M. Pérezpeña and
A. S. Morrissy and F. M. G. Cavalli and X. Wu and C. Daniels
and J. N. Rich and S. J. M. Jones and R. A. Moore and M. A.
Marra and X. Huang and J. Reimand and P. H. Sorensen and R.
J. Wechsler-Reya and W. A. Weiss and T. J. Pugh and L.
Garzia and C. L. Kleinman and L. D. Stein and N. Jabado and
D. Malkin and O. Ayrault and J. A. Golden and D. W. Ellison
and B. Doble and V. Ramaswamy and T. E. Werbowetski-Ogilvie
and H. Suzuki and K. J. Millen and M. D. Taylor},
title = {{F}ailure of human rhombic lip differentiation underlies
medulloblastoma formation.},
journal = {Nature},
volume = {609},
number = {7929},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2022-02264},
pages = {1021-1028},
year = {2022},
note = {2022 Sep;609(7929):1021-1028},
abstract = {Medulloblastoma (MB) comprises a group of heterogeneous
paediatric embryonal neoplasms of the hindbrain with strong
links to early development of the hindbrain1-4. Mutations
that activate Sonic hedgehog signalling lead to Sonic
hedgehog MB in the upper rhombic lip (RL) granule cell
lineage5-8. By contrast, mutations that activate WNT
signalling lead to WNT MB in the lower RL9,10. However,
little is known about the more commonly occurring group 4
(G4) MB, which is thought to arise in the unipolar brush
cell lineage3,4. Here we demonstrate that somatic mutations
that cause G4 MB converge on the core binding factor alpha
(CBFA) complex and mutually exclusive alterations that
affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is
expressed early in the progenitor cells of the cerebellar RL
subventricular zone in Homo sapiens, and G4 MB
transcriptionally resembles these progenitors but are
stalled in developmental time. Knockdown of OTX2 in model
systems relieves this differentiation blockade, which allows
MB cells to spontaneously proceed along normal developmental
differentiation trajectories. The specific nature of the
split human RL, which is destined to generate most of the
neurons in the human brain, and its high level of
susceptible EOMES+KI67+ unipolar brush cell progenitor cells
probably predisposes our species to the development of G4
MB.},
cin = {B062},
ddc = {500},
cid = {I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36131014},
doi = {10.1038/s41586-022-05215-w},
url = {https://inrepo02.dkfz.de/record/181849},
}