Landscape Of Idh1/2 Mutations In Chinese Patients With Solid Tumors: A Pan-Cancer Analysis

Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan-cancer has not been fully characterized.Methods: Tissue or blood samples were subjected to next-generation sequencing (NGS) for detection the IDH mutation.Results: A total of 28.868 patients from more than 20 solid tumor species were analyzed. A total of 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer (BTC), 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer, and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. However, there were significant differences in IDH1 and IDH2 mutation frequency among different tumor species (p = 0.0003). Of the patients with IDH1 mutations, about 53.0% of these mutations occur in codons 132. Codons 172 (25.4%) was high-frequency mutation subtypes in IDH2 mutation. TP53, PBRM1, and BAP1 were the most significantly mutated genes in BTC which were different from others cancer. Moreover, TMB were significantly higher in lung cancer, colorectal cancer, and gastric cancer than BTC (p = 0.0164, p < 0.0001, p = 0.0067, respectively) and BTC patients with IDH mutation had lower TMB compared with wild-type IDH.Conclusion: Somatic IDH mutation was found in multiple solid tumors and IDH would be a driver gene in BTC.