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000296130 1001_ $$aLee, John J. Y.$$b0
000296130 245__ $$aZIC1 is a context-dependent medulloblastoma driver in the rhombic lip
000296130 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2025
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000296130 520__ $$aTranscription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma ZIC1 mutants exhibit LOF phenotypes. Distinct ZIC1 mutations affect cells of the rhombic lip in diametrically opposed ways, suggesting that ZIC1 is a critical developmental transcriptional regulator in both the normal and transformed rhombic lip and identifying ZIC1 as an exquisitely context-dependent driver gene in medulloblastoma.
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000296130 7001_ $$00000-0002-0578-4823$$aYou, Zhen$$b2
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000296130 7001_ $$00000-0002-6134-7812$$aErickson, Anders W.$$b4
000296130 7001_ $$aFarooq, Hamza$$b5
000296130 7001_ $$aHendriske, Liam D.$$b6
000296130 7001_ $$aAbeysundara, Namal$$b7
000296130 7001_ $$aRichman, Cory M.$$b8
000296130 7001_ $$00000-0001-7984-3147$$aWang, Evan Y.$$b9
000296130 7001_ $$aDas Gupta, Neha$$b10
000296130 7001_ $$00000-0003-1918-747X$$aHadley, Jennifer$$b11
000296130 7001_ $$00009-0007-3130-6570$$aBatts, Melissa$$b12
000296130 7001_ $$aMount, Christopher W.$$b13
000296130 7001_ $$aWu, Xiaochong$$b14
000296130 7001_ $$aRasnitsyn, Alex$$b15
000296130 7001_ $$aBailey, Swneke$$b16
000296130 7001_ $$aCavalli, Florence M. G.$$b17
000296130 7001_ $$00000-0001-8526-562X$$aMorrissy, Sorana$$b18
000296130 7001_ $$00000-0002-5016-0753$$aGarzia, Livia$$b19
000296130 7001_ $$aMichealraj, Kulandaimanuvel Antony$$b20
000296130 7001_ $$aVisvanathan, Abhi$$b21
000296130 7001_ $$aFong, Vernon$$b22
000296130 7001_ $$aPalotta, Jonelle$$b23
000296130 7001_ $$aSuarez, Raul$$b24
000296130 7001_ $$00000-0003-4947-0081$$aLivingston, Bryn G.$$b25
000296130 7001_ $$aLiu, Miao$$b26
000296130 7001_ $$aLuu, Betty$$b27
000296130 7001_ $$aDaniels, Craig$$b28
000296130 7001_ $$aLoukides, James$$b29
000296130 7001_ $$aBendel, Anne$$b30
000296130 7001_ $$00000-0002-0668-9529$$aFrench, Pim J.$$b31
000296130 7001_ $$00000-0002-4727-0724$$aKros, Johan M.$$b32
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000296130 7001_ $$00000-0002-6802-1102$$aHamilton, Ronald L.$$b53
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