What is an IDH mutation?

Mutations in the genes encoding the cytoplasmic and mitochondrial forms of isocitrate dehydrogenase (IDH1 and IDH2, respectively; collectively referred to as IDH) are frequently detected in cancers of various origins, including but not limited to acute myeloid leukaemia (20%), cholangiocarcinoma (20%), chondrosarcoma ( …

Is IDH mutation good or bad?

Many studies showed that patients with IDH-mut gliomas have better survival compared to their IDH-wt counterparts irrespective of histology and grade, making IDH mutation the most important prognostic factor for survival, followed by age, tumor grade, and O6-methylguanine-DNA methyltransferase gene (MGMT) status ( …

What causes IDH mutations?

IDH mutations are found in about one-quarter of people with acute myeloid leukemia (AML), the most common type of leukemia in adults. They may also be found in a type of bile duct cancer called cholangiocarcinoma, a bone cancer called chondrosarcoma, low-grade glioma, and some kinds of lymphoma.

What is IDH in cancer?

Isocitrate dehydrogenase (IDH) is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Recurrent mutations in IDH1 or IDH2 are prevalent in several cancers including glioma, acute myeloid leukemia (AML), cholangiocarcinoma and chondrosarcoma.

What is IDH mutant glioblastoma?

IDH mutant glioblastoma is the final stage of malignant progression from an IDH mutant diffuse astrocytoma (WHO grade II) or IDH mutant anaplastic astrocytoma (WHO grade III) (J Clin Oncol 2011;29:4482)

What is IDH mutant glioma?

Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target.

What is IDH in glioblastoma?

Abstract. Isocitrate dehydrogenase (IDH) is a key rate-limiting enzyme in the Krebs cycle that plays an important role in energy metabolism. In recent years, it has been found that IDH mutations are closely related to the occurrence and development of glioma, and it is a notable potential therapeutic target.

What does IDH negative mean?

IDH-wild-type = IDH negative = no mutation = poor prognosis. IDH-mutant = IDH positive = mutation present = better prognosis.

What is the importance of the IDH mutation in the case of glioblastoma?

Importantly, IDH1R132H confers a distinctive survival advantage in glioma patients; large cohort studies confirmed a 2-fold increase of median overall survival in glioblastoma patients and a more than threefold increase in lower-grade glioma patients compared with their respective controls (11,19).

What is the IDH mutation used for?

IDH mutations are valuable diagnostic marker that helps the differential diagnosis of low-grade glioma from reactive gliosis and other IDH-wild type tumour entities 16. Indeed, the presence of the IDH mutation is a pathognomonic biomarker that indicates a glioma entity in the setting of brain tumours.

Is IDH1 mutation an inclusion criterion in clinical trials for malignant solid tumor?

IDH1 Mutation is an inclusion criterion in 10 clinical trials for malignant solid tumor, of which 8 are open and 2 are closed. Of the trials that contain IDH1 Mutation and malignant solid tumor as inclusion criteria, 5 are phase 1 (3 open) and 5 are phase 2 (5 open) [ 5 ].

What is the pathophysiology of IDH-mutant gliomas?

Molecular studies of IDH-mutant gliomas have established that the IDH mutation is an early causative event in the pathogenesis of this brain tumour subset 12,14. Accordingly, the IDH mutation is often referred as a “trunk” (or initiating) event in the clonal evolutionary tree of IDH-mutant gliomas.

Where are the IDH1 and IDH2 genes located?

The IDH1 and IDH2 genes are located on chromosome 2q33.3 and 15q26.1, respectively. Mutations in the IDH1 and IDH2 genes have been identified in subsets of patients across a number of solid and haematologic malignancies, including glioma, acute myeloid leukaemia, myelodysplastic sybdrome, cholangiosarcoma and chondrosarcoma.