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

Abstract

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.

Computer 3D Scene Simulation of Ecological Landscape Layout Planning

“…Because of its simple structure, the vertex shader only defines the vertex position of each level of the branch, the index of the upper level of the branch, and the length of the branch, and draws the appearance of the branch through the transformation of the corresponding vertex data. In the slice shader, all levels of branch nodes with vertex positions are uniformly drawn, and the corresponding branch texture maps are speci ed to realize the rendering of realistic tree branches at all levels [23].…”

Biology of IDH mutant cholangiocarcinoma

“…[101][102][103] More broadly, the frequency of IDH mutation is particularly high in iCCA among gastrointestinal cancers and epithelial malignancies in general. [101,104] iCCAs also have a distinct spectrum of specific mIDH mutant alleles, favoring variants that generate highest levels of 2HG-with the potent IDH1-R132C and IDH2-R172K alleles accounting for >70% of the IDH1 mutations and >40% of the IDH2 mutations, respectively. [47][48][49]101,102] The R132H allele, which is the most common IDH1 mutation in glioma and comprises ~25% of mIDH1 AML, accounts for only ~1% of mIDH1 iCCAs.…”