Jialing Huang1,2, Li-Hui Tseng1,3, Vamsi Parini1, Parvez M Lokhandwala1, Aparna Pallavajjala1, Erika Rodriguez1, Rena Xian1,4, Liam Chen1, Christopher D Gocke1,4, James R Eshleman1,4, Ming-Tseh Lin1.
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. © American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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. © American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities:
Keywords:
zzm321990 BRAF p.V600E; zzm321990 IDH1zzm321990 ; zzm321990 IDH2zzm321990 ; Colitis-associated cancer; Colorectal cancer
Mesh：
Substances：
Year: 2021
PMID： 33929516 DOI： 10.1093/ajcp/aqab023
Source DB: PubMed Journal: Am J Clin Pathol ISSN： 0002-9173 Impact factor: 5.400