Q (sonnet-5.5): what do idh1 mutations do?

═ answer (success)
Note: this is general background knowledge, not something computed from cBioPortal data. cBioPortal holds mutation and clinical data, so it can't tell you what a mutation does biologically.

**Background on IDH1 mutations**
- The recurrent hotspot is R132 (most often R132H). It is a heterozygous, gain-of-function change in the isocitrate dehydrogenase 1 enzyme.
- The normal enzyme converts isocitrate to α-ketoglutarate. The mutant enzyme gains a new activity: it converts α-ketoglutarate to the "oncometabolite" 2-hydroxyglutarate (2-HG).
- 2-HG accumulates and inhibits α-KG-dependent dioxygenases, including TET DNA demethylases and histone demethylases. This leads to a hypermethylated (CpG island methylator) phenotype and a block in cell differentiation.
- These mutations are characteristic of lower-grade glioma and secondary glioblastoma. They also occur in AML, cholangiocarcinoma, and chondrosarcoma.

**What I can pull from cBioPortal**
- IDH1 mutation frequency by cancer type or in a specific study, such as TCGA lower-grade glioma or GBM.
- The variant breakdown, for example the share of R132H versus other R132 changes.
- Counts of IDH1-mutant versus wild-type samples, with a link to a Group Comparison for survival or clinical differences.

Tell me which cancer type or study you're interested in, and I'll run the query and give you links.