{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324649/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324649"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Effect of CALCOCO2 depletion in HDMB03 Group 3 medulloblastoma cells","description":"Medulloblastoma (MB) is the most common malignant paediatric brain tumour, with Group 3 disease representing the most aggressive and therapy-refractory subtype. Despite intensive craniospinal radiotherapy, outcomes remain poor and the molecular basis of radioresistance is unclear. Here we identify CALCOCO2 as a key determinant of Group 3 MB aggressiveness and radiotherapy resistance. CALCOCO2 is markedly upregulated in Group 3 tumours, where high expression correlates with adverse clinical outcome. We show that CALCOCO2 is transcriptionally regulated by the developmental factor OTX2, defining a previously unrecognised axis that sustains a progenitor-like, transformation-permissive state. Functionally, nuclear CALCOCO2 promotes efficient repair of radiation-induced DNA double-strand breaks by engaging POLθ-dependent alternative end joining. Disruption of the CALCOCO2–POLθ pathway impairs DNA repair, sensitizes tumour cells to radiotherapy and suppresses tumour growth in vitro and in vivo. These findings uncover a developmentally wired DNA repair dependency in Group 3 MB and highlight POLθ inhibition as a rational strategy to overcome therapeutic resistance.","dates":{"publication":"2026/09/01"},"accession":"GSE324649","cross_references":{"GSM":["GSM9581593","GSM9581595","GSM9581594","GSM9581597","GSM9581596"],"GPL":["24676"],"GSE":["324649"],"taxon":["Homo sapiens"]}}