IDH1 and IDH2 Mutations in Colorectal Cancers

Am J Clin Pathol. 2021 Oct 13;156(5):777-786. doi: 10.1093/ajcp/aqab023.


Objectives: To elucidate clinicopathologic and molecular characteristics of IDH1 and IDH2 (IDH1/2) mutations in colorectal cancers (CRCs).

Methods: We evaluated IDH1/2 mutations in 1,623 CRCs using a next-generation sequencing assay.

Results: IDH1/2 mutations, predominantly IDH1 p.R132C, were detected in 15 (0.9%) CRCs and in 5 (3.0%) of 167 BRAF p.V600E-mutated CRCs. Three IDH1/2-mutated CRCs were associated with inflammatory bowel disease. They were significantly associated with old age, mucinous or signet ring cell adenocarcinoma, and high-grade histomorphology. Concordance of variant allele frequency between IDH1/2 mutants and other trunk drivers in CRCs and presence of IDH1/2 mutation in the adenoma and early adenocarcinoma indicated IDH1/2 mutations could be trunk drivers suitable for targeted therapy.

Conclusions: IDH1/2 mutations in CRCs were uncommon but enriched in BRAF p.V600E-mutated CRCs and perhaps colitis-associated CRCs. Further studies on IDH1/2-mutated CRCs are needed to clarify their clinicopathologic features and implications for targeted therapy.

Keywords: BRAF p.V600E; IDH1; IDH2; Colitis-associated cancer; Colorectal cancer.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Sequence Analysis, DNA


  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human