What is IDH mutation 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 does IDH mutant mean?
Those with mutations in a gene known as IDH, for example, are linked to much longer survival, regardless of the cancer’s stage at diagnosis. In fact, clinicians often look for this molecular detail when patients are first diagnosed.
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 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).
Who glioblastoma IDH?
In glioma, IDH mutations are recognised in >80% of World Health Organisation (WHO) grade II/III cases. In WHO grade IV glioblastoma (GBM), IDH mutations are also found frequent in secondary GBM, which account for 73% of clinical cases, whereas they are less seen in primary GBM (3.7%).
Why is IDH important?
These studies demonstrated that in addition to being a major enzyme in the citric acid cycle, IDH may also function to maintain the cellular redox state and suggests that IDH plays an important role in cellular defense against oxidative stress.
What is IDH wild type glioblastoma?
IDH-wildtype glioblastoma is a relatively common malignant brain tumor in adults. These patients generally have dismal prognoses, although outliers with long survival have been noted in the literature.
What is an IDH inhibitor?
IDH inhibitors alter the activity of IDH enzymes, resulting in reduction of α-ketoglutarate (KG) to D-2-hydroxyglutarate (2-HG), a competitive inhibitor of α-KG.
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 does IDH negative mean?
IDH-wild-type = IDH negative = no mutation = poor prognosis. IDH-mutant = IDH positive = mutation present = better prognosis.
What is the difference between glioblastoma and glioblastoma multiforme?
Glioblastoma, sometimes referred to as glioblastoma multiforme (GBM), is considered a grade IV tumor. They are the most aggressive and are very infiltrative — they spread into other parts of the brain quickly. Glioblastomas don’t metastasize (or spread) outside of the brain.
What is IDH2 mutation?
The IDH2 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. These mutations change single protein building blocks (amino acids) in the isocitrate dehydrogenase 2 enzyme.
How are IDH1 and IDH2 mutations related to gliomas?
IDH mutations are oncogenic, although whether the mechanism is through alterations in hydroxylases, redox potential, cellular metabolism, or gene expression is not clear. The mutations also drive increased methylation in gliomas. Gliomas with mutated IDH1 and IDH2 have improved prognosis compared to gliomas with wild-type IDH.
Are there any mutations in the metabolic gene IDH1?
In 2008, a multi-group collaboration sequenced over 20,000 genes in 22 GBMs and identified a common point mutation in the metabolic gene IDH1 in 12% of the samples analyzed [7]. Further studies found that this mutation is present in ~80% of grade II-III gliomas and secondary GBM [8-14].
How old do you have to be to have an IDH mutation?
People with gliomas with mutated IDH are, on average, several years younger than people with gliomas with wild-type IDH. On the other hand, IDH mutations are rare in gliomas in young children, although they are common in gliomas in adolescents 14 years-old or older [54, 55].
Are there idh1mutations in Grade II astrocytomas?
Several lines of evidence suggest that IDH1mutations are an early event in glioma development. As described above, IDH1 mutations are seen in a high percentage of grade II and III astrocytomas and oligodendrogliomas and secondary GBM tumors.