Correspondence (letter to the editor): Isocitrate Dehydrogenase Genes

The molecular classification and taxonomy of malignant diseases, such as the one successfully applied and published by The Cancer Genome Atlas Project TCGA (http://cancergenome.nih.gov/) for urinary bladder and colorectal cancer, adenocarcinoma of the stomach, and glioblastoma multiforme, provides the opportunity to define so-called driver mutations for the various entities and hence to predict the efficacy of drugs and the clinical prognosis. With the recent completion of the specimen collection for cholangiocarcinoma, publication of the results is to be expected in the near future. In an insightful review (1), the authors listed 13 genes which are involved in certain cellular signaling pathways and can be influenced by targeted treatment. Using the latest generation of genome sequencing techniques, promising potential applications were identified for the FGFR and ROS1 signaling pathways and mutations of the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes (2). The latter is very important for two reasons: Of all malignant entities of the gastrointestinal tract, the IDH mutations are only identified in cholangiocarcinoma. The oncometabolite 2-hydroxyglutarate is the product of this mutated enzyme and has been identified as potential surrogate biomarker in patients with cholangiocarcinoma (3). In addition, this marker offers the advantage over the commonly used serum levels of CA 19 – 9 that its concentration is not dependent on the Lewis and secretor genotypes of the blood groups. Cisplatin sensitivity of the cholangiocarcinoma is associated, as in the urinary bladder and non-small-cell lung cancer, with the somatic ERCC2 gene mutations.