Gene mutation

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Mutations range in size; they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes.

In genetics, a mutation is a permanent change of the nucleotide sequence of the genome of an organism, virus, or extrachromosomal genetic element. Mutations result from unrepaired damage to DNA or to RNA genomes (typically caused by radiation or chemical mutagens), errors in the process of replication, or from the insertion or deletion of segments of DNA by mobile genetic elements.

Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system.

It has been reiterated many times that molecular typing of (brain) tumors is more reliable and precise than histological classification, but data confirming this belief are largely missing. While it appears intuitive that searching for absence versus presence of a mutation is more straightforward and afflicted with less inter-rater variability than a diagnosis based on the bewildering variety of histological pictures, it still remains a hypothesis that needs to be tested in systematic inter-rater reliability studies.

Mutations in isocitrate dehydrogenase (IDH) 1 and 2, originally discovered in 2009, occur in the vast majority of low grade gliomas and secondary high-grade gliomas. These mutations, which occur early in gliomagenesis, change the function of the enzymes, causing them to produce 2-hydroxyglutarate, a possible oncometabolite, and to not produce NADPH. 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. Mutated IDH can now be detected by immunohistochemistry and magnetic resonance spectroscopy. No drugs currently target mutated IDH, although this remains an area of active research 1).

Gliomas, the most common primary brain tumors, are characterized by isocitrate dehydrogenase 1 mutation (IDH1-M). High mutation frequency of IDH1 indicates it's promoting role in tumorgenesis. However, the observation that patients with IDH1-M have better survival comparing with patients with IDH1 wild-type (IDH1-W) suggests that this alteration has other significant beneficial features for patients.

Mutation nomenclature

Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep. 2013 May;13(5):345. doi: 10.1007/s11910-013-0345-4. Review. PubMed PMID: 23532369; PubMed Central PMCID: PMC4109985.
  • gene_mutation.txt
  • Last modified: 2022/01/13 13:23
  • by administrador