Landscape of IDH mutations in patients with solid tumors: A pan-cancer analysis.

e13638 Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle, including IDH1-3. Mutations in IDH family are common in glioma and hematologic malignancies. IDH inhibitors have shown promising efficacy not only in hematologic malignancies but also cholangiocarcinoma patients harboring IDH1 mutations. However, the landscape of IDH mutations in pan-cancer has not been fully characterized. Methods: Tissue or blood samples were subjected to NGS in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for detection the IDH mutation. Results: A total of 12,372 patients from more than 20 solid tumor species were analyzed, including biliary carcinoma (960 cases), liver cancer (1433 cases), lung cancer (3557 cases) and colorectal cancer (1310 cases). 105 cases (0.8%) with IDH mutations were identified. The average age for patients harboring IDH mutations was 59 years (range, 29-80 years). Among all the IDH mutations cases, 49 (47%) were biliary tract cancer, 25 (24%) were liver cancer, 16 (15%) were lung cancer and 7 (7%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 84 cases and 21 cases, respectively. IDH1 R132C mutation represents 45.7% (n = 48) of all IDH mutations. Other mutations found affecting either IDH1 at Arg132 included R132L (n = 24), R132G (n = 5), R132H (n = 5) and R132S (n = 2) or IDH2 at Arg172 (R172K most frequently). In addition, IDH1/2 gene was most frequently co-mutated with TP53 and ARID1A. Conclusions: Somatic IDH1/2 mutations are found in multiple solid tumors and patients with IDH1/2 mutations may benefit from IDH1/2 inhibitors in the future.