{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lee JJY"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","EIF | Stand Up To Cancer (SU2C)","U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)","NCI NIH HHS","NINDS NIH HHS","Wellcome Trust"],"pagination":["88-102"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11735403"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["57(1)"],"pubmed_abstract":["Transcription 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 mutan"],"journal":["Nature genetics"],"pubmed_title":["ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip."],"pmcid":["PMC11735403"],"funding_grant_id":["R01 CA255369","SU2C-AACR-DT1113","SU2C-AACR-DT-19-15","R01 CA159859","R01NS106155","1R01CA270785-01A1","R37 NS095733","R01 CA270785","R01CA255369","P01 CA096832","R01 NS106155"],"pubmed_authors":["Mount CW","Morrissy S","Kool M","Suva ML","Livingston BG","French PJ","Hendriske LD","Das Gupta N","Korshunov A","Phillips JJ","Thompson RC","Kros JM","Perek-Polnik M","Batts M","Visvanathan A","Kim SK","Wu X","Zadeh G","Taylor MD","Saad AG","Northcott PA","Garzia L","Gallo M","Bendel A","Abeysundara N","Cavalli FMG","Palotta J","Bailey S","Grajkowska WA","Lee JJY","Tominaga T","Ra YS","Huang LF","Weiss WA","Mack SC","Singh SK","Klekner A","Farooq H","Michealraj KA","Liu M","Ramaswamy V","Suzuki H","Wang EY","Lupien M","Richman CM","Bognar L","Kenney AM","Haldipur P","Loukides J","Fong V","Pollack IF","Jabado N","Cho BK","You Z","Millen KJ","Cooper MK","Hadley J","Lach B","Luu B","Suarez R","Daniels C","Erickson AW","Lee JY","Wang KC","Dai S","Rasnitsyn A","Leary SES","Chico Ponce de Leon F","Hamilton RL","Tao R","Perezpena-Diazconti M"],"additional_accession":[]},"is_claimable":false,"name":"ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.","description":"Transcription 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 mutan","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-06-01T21:07:11.98Z","creation":"2025-04-06T01:16:03.978Z"},"accession":"S-EPMC11735403","cross_references":{"pubmed":["39753768"],"doi":["10.1038/s41588-024-02014-z"]}}