NCH612

NCH612 is a patient-derived glioma cell line known to harbor a mutation in the IDH1 gene, specifically the IDH1 R132H variant. This mutation is often found in gliomas and is associated with epigenetic alterations such as the glioma CpG island methylator phenotype (G-CIMP). These epigenetic changes can lead to the silencing of tumor suppressor genes, making IDH1-mutant gliomas a target for epigenetic therapies. The NCH612 cell line shows particular sensitivity to the DNA methyltransferase inhibitor decitabine (DAC), which has demonstrated the ability to inhibit cell proliferation and growth by reducing DNMT1 protein levels, a key epigenetic regulator. NCH612, in particular, exhibits a partial deletion of the 1p/19q chromosome arms, a characteristic often associated with certain subtypes of gliomas. When treated with DAC, NCH612 cells show a significant reduction in cell proliferation and colony formation, as demonstrated in various assays. This sensitivity to DAC is linked to the downregulation of TERT (telomerase reverse transcriptase) and the upregulation of p21, a cyclin-dependent kinase inhibitor involved in the DNA damage response. Interestingly, NCH612 is one of several IDH1-mutant-codel glioma lines that exhibit this sensitivity, whereas other lines, such as NCH1681 (which lacks the 1p/19q codeletion), are resistant to DAC. This suggests that the therapeutic effects of DAC may be particularly pronounced in gliomas with both IDH1 mutations and 1p/19q deletions. Further molecular studies have shown that DAC treatment in NCH612 cells induces enrichment of pathways related to DNA replication, cell cycle regulation, and lysosome function, which are key to understanding the drug's antitumor effects. The repression of TERT by DAC is mediated by p21, and this interaction plays a crucial role in determining the cell's response to the drug. Given these characteristics, NCH612 is an important model for studying the effects of DNMT inhibitors like DAC in IDH1-mutant gliomas with 1p/19q codeletion. Brain cancer cell lines, Brain, Anaplastic oligodendroglioma, WHO grade III, IDH1 mutant (R132H), Growth Conditions: Spheroid culture, Biosafety level: BSL 1