Isocitrate dehydrogenase 1 gene mutations: a case review unveiling its biological impact on disease progression, prognosis and treatment in Chilean patients

Isocitrate dehydrogenase 1 gene (IDH1, [NADP (+)] 1) encodes for an enzyme that catalyses the oxidative decarboxylation of isocitrate into α-ketoglutarate. However, it is well known that mutant IDH1 (mu/IDH1) promotes the accumulation of D2-hydroxyglutarate, an oncometabolite that stimulates tumourigenesis through various secondary, complex metabolic effects. IDH1 and also IDH2 gene mutations have been identified in several types of cancers, such as gliomas, conventional central and periosteal malignant cartilaginous tumours, cytogenetically normal acute myeloid leukaemia, and cholangiocarcinoma. Here, we present 4 cases of Chilean patients with different primary malignant tumours harbouring IDH1. One patient carried the IDH1 p. R132H mutation, the other has IDH1 p. R132L mutation, and the last 2, IDH1 p. R132C mutation. Of note, all these patients had a very poor response to chemotherapy and a rapid disease progression, resulting in a relatively swift death. Next-Generation Sequencing results highlighting mutations in those genes, and other cancer genes were further subjected to in silico study of protein-protein interactions, gene ontology, and pathway enrichment. We also include a state-of-the-art literature review about IDH1 and IDH2 molecular biology, biochemical properties, and the role of their mutations in cancer development and progression, along with insights into regional variations in cancer biology and treatment response.