Omics · study · 2026
Effect of CALCOCO2 depletion in HDMB03 Group 3 medulloblastoma cells
Listed in NCBI GEO
Medulloblastoma (MB) is the most common malignant paediatric brain tumour, with Group 3 disease representing the most aggressive and therapy-refractory subtype.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324649 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324649 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1436480 ncbi.nlm.nih.gov/bioproject/PRJNA1436480 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE324649 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |