Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, Thomas Jefferson University, Philadelphia, PA, USA.
Am J Clin Pathol. 2021 Oct 13;156(5):777-786. doi: 10.1093/ajcp/aqab023.
To elucidate clinicopathologic and molecular characteristics of IDH1 and IDH2 (IDH1/2) mutations in colorectal cancers (CRCs).
We evaluated IDH1/2 mutations in 1,623 CRCs using a next-generation sequencing assay.
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.
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.
阐明 IDH1 和 IDH2（IDH1/2）突变在结直肠癌（CRC）中的临床病理和分子特征。
我们使用下一代测序检测了 1623 例 CRC 中的 IDH1/2 突变。
在 15 例（0.9%）CRC 和 167 例 BRAF p.V600E 突变的 CRC 中的 5 例（3.0%）中检测到 IDH1/2 突变，主要为 IDH1 p.R132C。3 例 IDH1/2 突变的 CRC 与炎症性肠病相关。它们与老年、黏液性或印戒细胞腺癌以及高级别组织形态学显著相关。CRC 中 IDH1/2 突变体与其他主干驱动基因的变异等位基因频率的一致性以及腺瘤和早期腺癌中存在 IDH1/2 突变表明 IDH1/2 突变可能是适合靶向治疗的主干驱动基因。
CRC 中的 IDH1/2 突变不常见，但在 BRAF p.V600E 突变的 CRC 中更为丰富，可能在结肠炎相关的 CRC 中也更为丰富。需要进一步研究 IDH1/2 突变的 CRC，以阐明其临床病理特征及其对靶向治疗的意义。
