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.