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 (, [NADP (+)] 1) encodes for an enzyme that catalyses the oxidative decarboxylation of isocitrate into α-ketoglutarate. However, it is well known that mutant (mu/1) promotes the accumulation of D2-hydroxyglutarate, an oncometabolite that stimulates tumourigenesis through various secondary, complex metabolic effects. and also 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 . One patient carried the p. R132H mutation, the other has p. R132L mutation, and the last 2, 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 study of protein-protein interactions, gene ontology, and pathway enrichment. We also include a state-of-the-art literature review about and 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.