IDH1 is an enzyme localized to the cytoplasm and peroxisomes and involved in citrate metabolism. IDH-mutant tumors have aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in several malignancies including AML, central nervous system and biliary tract. Strikingly, IDH1 mutations were rarely detected in the other solid tumor types. While IDH1 mutations have been reported in 1-2% of lung adenocarcinomas, the clinical significance of this mutation with regards to response to anti-IDH1 therapy in lung cancer is unknown. This specific IDH1 p.PR119Q has been identified in numerous reports, but it has not been biochemically characterized and its effect on protein function is unknown. Results should be interpreted in conjunction with other laboratory and clinical findings.
- Imielinski M, et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150(6):1107-20
- Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511(7511):543-50
- Losman JA, et al. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev 2013;27(8):836-52
- Cohen AL, et al. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep 2013;13(5):345
- Patel JP, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366(12):1079-89
- Borger DR, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist 2012;17(1):72-9
- Sequist LV, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 2011;22(12):2616-24
- Guan L, Gao L, Wang L, Li M, Yin Y, Yu L, Gao C. The frequency and clinical significance of IDH1 mutations in Chinese acute myeloid leukemia patients. PloS one. 2013 Dec 20;8(12)