Analysis of IDH1 and IDH2 mutations as causes of the hypermethylator phenotype in colorectal cancer.

ABSTRACT: The CpG island methylator phenotype (CIMP) occurs in many colorectal cancers (CRCs). CIMP is closely associated with global hypermethylation and tends to occur in proximal tumours with microsatellite instability (MSI), but its origins have been obscure. A few CRCs carry oncogenic (gain-of-function) mutations in isocitrate dehydrogenase IDH1. Whilst IDH1 is an established CRC driver gene, the low frequency of IDH1-mutant CRCs (about 0.5%) has meant that the effects and molecular covariates of those mutations have not been established. We first showed computationally that IDH2 is also a CRC driver. Using multiple public and in-house CRC datasets, we then identified IDH mutations at the hotspots (IDH1 codons 132 and IDH2 codons 140 and 172) frequently mutated in other tumour types. Somatic ID

SUBMITTER: Ward JC 

PROVIDER: S-EPMC12337813 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature