IDH1 and IDH2 Mutations in Colorectal Cancers

Jialing Huang; Li-Hui Tseng; Vamsi Parini; Parvez M Lokhandwala; Aparna Pallavajjala; Erika Rodriguez; Rena Xian; Liam Chen; Christopher D Gocke; James R Eshleman; Ming-Tseh Lin

doi:10.1093/ajcp/aqab023

IDH1 and IDH2 Mutations in Colorectal Cancers

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

Authors

Jialing Huang^{1

2}, Li-Hui Tseng^{1

3}, Vamsi Parini¹, Parvez M Lokhandwala¹, Aparna Pallavajjala¹, Erika Rodriguez¹, Rena Xian^{1

4}, Liam Chen¹, Christopher D Gocke^{1

4}, James R Eshleman^{1

4}, Ming-Tseh Lin¹

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA.
³ Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
⁴ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 33929516
DOI: 10.1093/ajcp/aqab023

Abstract

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

Substances

IDH2 protein, human
Isocitrate Dehydrogenase
IDH1 protein, human