Abstract 76P
Background
Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. In addition to gliomas and acute myeloid leukemia, IDH mutations have been found in approximately 75% of chondrosarcomas, 10-23% of biliary tract cancer (BTC), and a small number of other tumors. IDH inhibitors have shown promising efficacy in cholangiocarcinoma patients harboring IDH1 mutations. However, the distribution of tumor mutational burden in IDH-mutant solid tumors has not been fully characterized.
Methods
Tissue 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 317 IDH mutated patients from 5 solid tumor species were analyzed, including biliary carcinoma (81 cases), liver cancer (66 cases), lung cancer (85 cases), colorectal cancer (61 cases) and gastric cancer (24 cases). The average age for patients harboring IDH mutations was 60 years (range, 25-86 years). Among all the IDH mutations cases, the most common IDH variant were IDH1 and IDH2 which were discovered in 183 cases (57.7%) and 106 cases (33.4%), respectively. The TMB were significantly higher in lung cancer, colorectal cancer and gastric cancer than BTC (p= 0.0164, p <0.0001, p= 0.0067, respectively). In addition, we also analyzed the relationship between IDH mutation/wild-type with TMB in BTC (n=907). Patients with IDH mutation (n=72) had lower TMB compared with patients with wild-type IDH (p= 0.0236).
Conclusions
Our findings suggest that IDH mutation may be a potential driving mutation gene of BTC which can independently lead to the development of tumor. But in other tumors it may be only co-mutation gene.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Bai: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.