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  1. Ali RH, Alateeqi M, Jama H, Alrumaidhi N, Alqallaf A, Mohammed EM, et al.
    J Clin Pathol, 2023 Feb;76(2):103-110.
    PMID: 34489310 DOI: 10.1136/jclinpath-2021-207876
    AIMS: Accurate assessment of 1p/19q codeletion status in diffuse gliomas is of paramount importance for diagnostic, prognostic and predictive purposes. While targeted next generation sequencing (NGS) has been widely implemented for glioma molecular profiling, its role in detecting structural chromosomal variants is less well established, requiring supplementary informatic tools for robust detection. Herein, we evaluated a commercially available amplicon-based targeted NGS panel (Oncomine Comprehensive Assay v3) for the detection of 1p/19q losses in glioma tissues using an Ion Torrent platform and the standard built-in NGS data analysis pipeline solely.

    METHODS: Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard.

    RESULTS: The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (p<0.001). NGS was concordant with FISH and was superior to it in distinguishing partial from contiguous losses indicative of whole-arm chromosomal deletion.

    CONCLUSIONS: This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH.

    Matched MeSH terms: Isocitrate Dehydrogenase/genetics
  2. Jayapalan RR, Mun KS, Wong KT, Sia SF
    World Neurosurg X, 2019 Apr;2:100006.
    PMID: 31218281 DOI: 10.1016/j.wnsx.2018.100006
    Background: Rosette-forming glioneuronal tumor (World Health Organization grade I) is considered as a benign tumor with very low potential for progression. The potential for malignant transformation of this tumor is not known and has never been reported before in literature.

    Case Description: We report a 42-year-old man, diagnosed with rosette-forming glioneuronal tumor of the fourth ventricle with a positive isocitrate dehydrogenase 1 mutation, progressed to glioblastoma after 6 years from diagnosis. We discuss the clinical history, radiological findings, and histopathological characteristic with immunohistochemistry findings observed in this unique case.

    Conclusions: Despite being acceptable as benign, based on our observations in this case, there is a potential for malignant transformation of rosette-forming glioneuronal tumor. The role of isocitrate dehydrogenase 1 mutation leading to malignant transformation could not be established as our finding is novel and further prospective studies are required to prove this association.

    Matched MeSH terms: Isocitrate Dehydrogenase
  3. Abdul Aziz Mohamed Yusoff, Wan Salihah Wan Abdullah, Alarmelu Nithya Ramanathan, Jafri Malin Abdullah, Zamzuri Idris
    MyJurnal
    Although the precise etiology of Glioblastoma multiforme (GBM, WHO grade IV) remains unknown, its progression
    is believed to be driven by the accumulation of multiple genetic alterations. Here, we report a case of a patient who
    developed GBM, and associated with dual alterations, particularly 4977-bp deletion in mtDNA (mtDNA4977) and
    p.Arg132His (R132H) mutation in IDH1. A 35-year old Malaysian woman patient who primary diagnosed with astrocytoma WHO grade I and subsequently after four years developed a GBM, was detected with a mtDNA4977. This
    deletion appears to be a sporadic mutation. Additionally, analysis of patient’s tumor tissue also found to harbor a heterozygous IDH1 R132H mutation. This represents the first case report of coexisting mtDNA4977 together with IDH1
    R132H mutation in a Malaysian patient of GBM. The findings of dual alterations could be of therapeutic benefit if
    these alterations were justified to be contributing to GBM growth and aggressiveness.
    Matched MeSH terms: Isocitrate Dehydrogenase
  4. Wynn JP, Hamid AA, Li Y, Ratledge C
    Microbiology (Reading), 2001 Oct;147(Pt 10):2857-2864.
    PMID: 11577164 DOI: 10.1099/00221287-147-10-2857
    The biochemical events associated with the onset of lipid accumulation in Mucor circinelloides and Mortierella alpina, under conditions of nitrogen-limited growth, have been elucidated; they differ in key aspects from those described in oleaginous yeasts. The NAD+:isocitrate dehydrogenases of Mc. circinelloides and Mort. alpina were not absolutely dependent on AMP for activity. Furthermore, changes in the cellular adenine nucleotide pools and energy charge were different from those reported for oleaginous yeasts. In Mc. circinelloides ATP, ADP and AMP concentrations all decreased by 50% after nitrogen limitation, leading to a constant energy charge at the expense of the size of the total adenylate pool. Pyruvate carboxylase in Mc. circinelloides was cytosolic, having implications for the organization of lipid synthesis in filamentous fungi. As a result of the data obtained, a revised and more concerted mechanism for the initiation of storage lipid accumulation is put forward for filamentous fungi.
    Matched MeSH terms: Isocitrate Dehydrogenase/metabolism
  5. Johanson RA, Reeves HC
    Biochim. Biophys. Acta, 1977 Jul 08;483(1):24-34.
    PMID: 18195
    Oxalacetate and glyoxylate are each weak inhibitors of NADP+-specific isocitrate dehydrogenase (threo-DS-isocitrate:NADP+ oxidoreductase (decarboxylating), EC 1.1.1.42)9 Together, however, they act in a concerted manner and strongly inhibit the enzyme. The rates of formation and dissociation of the enzyme inhibitor complex, and the rate of formation and the stability of the aldol condensation product of oxalacetate and glyoxylate, oxalomalate, were examined. The data obtained do not support the often suggested possibility that oxalomalate, per se, formed non-enzymatically in isocitrate dehydrogenase assay mixtures containing oxalacetate and glyoxylate, is responsible for the observed inhibition of the enzyme. Rather, the data presented in this communication suggest that oxalacetate binds to the enzyme first, and that the subsequent binding of glyoxylate leads to the formation of a catalytically inactive enzyme-inhibitor complex.
    Matched MeSH terms: Isocitrate Dehydrogenase/antagonists & inhibitors*
  6. Taha EM, Omar O, Yusoff WM, Hamid AA
    Annals of microbiology, 2010 Dec;60(4):615-622.
    PMID: 21125005
    Lipid biosynthesis and fatty acids composition of oleaginous zygomycetes, namely Cunninghamella bainieri 2A1, cultured in media with excess or limited nitrogen were quantitatively determined at different times of culture growth. Accumulation of lipids occurred even when the activity of NAD(+)-ICDH (β-Nicotinamide adenine dinucleotide-isocitrate dehydrogenase) was still detectable in both media. In C. bainieri 2A1, under nitrogen limitation, the ratio of lipids was around 35%, whereas in nitrogen excess medium (feeding media supplemented with ammonium tartarate), the lipid ratio decreased. The amount of this decrease depended on the level of ammonium tartarate in the media. The main findings in this paper were that C. bainieri 2A1 has the ability to accumulate lipid although nitrogen concentration detected inside the media and that NAD-ICDH was active in all culture periods. These results proved that the strain C. bainieri 2A1 has an alternative behavior in lipid biosynthesis that differs from yeast. According to the old hypotheses, yeasts could not accumulate lipid more than 10% when nitrogen was detected inside the media. Nitrogen-limited and excess media both contained the same fatty acids (palmitic acid, stearic acid, olic acid, linoleic acid and γ-linolenic acid), but at different concentrations. The C:N ratio was also studied and showed no effects on total lipid accumulation, but a significant effect on γ-linolenic acid concentration.
    Matched MeSH terms: Isocitrate Dehydrogenase
  7. Mohamed Yusoff AA, Zulfakhar FN, Sul’ain MD, Idris Z, Abdullah JM
    Asian Pac J Cancer Prev, 2016 12 01;17(12):5195-5201.
    PMID: 28125199
    Background: Brain tumors, constituting one of the most deadly forms of cancer worldwide, result from the accumulation of multiple genetic and epigenetic alterations in genes and signaling pathways. Isocitrate dehydrogenase enzyme isoform 1 (IDH1) mutations are frequently identified in primary brain tumors and acute myeloid leukemia. Studies on IDH1 gene mutations have been extensively performed in various populations worldwide but not in Malaysia. This work was conducted to study the prevalence of IDH1 c.395G>A (R132H) hotspot mutations in a group of Malaysian patients with brain tumors in order to gain local data for the IDH1 mutation profile in our population. Methods: Mutation analysis of c.395G>A (R132H) of IDH1 was performed in 40 brain tumor specimens by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) and then verified by direct sequencing. Associations between the IDH1 c.395G>A (R132H) mutation and clinicopathologic characteristics were also analyzed. Results: The IDH1 c.395G>A (R132H) mutation was detected in 14/40 patients (35%). A significant association was found with histological tumor types, but not with age, gender and race. Conclusions: IDH1 is frequently mutated and associated with histological subtypes in Malay brain tumors.
    Matched MeSH terms: Isocitrate Dehydrogenase
  8. Bon MC
    Electrophoresis, 1996 Jul;17(7):1248-52.
    PMID: 8855412
    A combination of a modified Feret' (Silvae Genet. 1971, 20, 46-50) extraction buffer and two types of electrophoresis with acrylamide and starch gels were used to characterize allozymes in mature vegetative tissue of a commercially high value species of rattans (Calamus subinermis). From the analysis of allelic segregation from single maternal rattans and their offspring, genetic control of the 16 observed banding zones, which were consistently scorable, was assumed. Seventeen gene loci were identified. The percentage of polymorphic loci within Calamus subinermis was much higher (70.5%) than expected levels of genetic diversity for tropical woody and non-woody species. It is thought that the protocol described may be applied to the analysis of the genetic diversity of all the endangered Calamus species.
    Matched MeSH terms: Isocitrate Dehydrogenase/analysis; Isocitrate Dehydrogenase/genetics
  9. Ji H, Om AD, Yoshimatsu T, Umino T, Nakagawa H, Sakamoto S
    Fish Physiol Biochem, 2010 Sep;36(3):749-755.
    PMID: 19685218 DOI: 10.1007/s10695-009-9349-z
    To assess the effect of dietary ascorbate on lipid metabolism, 1-year black sea bream (Acanthopagrus schlegelii) were reared on a casein-based purified diet and an ascorbate fortified diet (1,100 mg of L: -ascorbyl-2- monophosphate-Mg/kg diet). The fortified ascorbate was effectively incorporated into the fish body and elevated muscle carnitine content. Fortifications of dietary ascorbate depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancreas and intraperitoneal fat body. Starvation after feeding experiment activated carnitine palmitoyltransferase as a lipolysis enzyme in the hepatopancreas in both control and vitamin C(VC) groups, while the lipolysis activity was significantly higher in VC group. These results confirmed that dietary ascorbate depressed lipogenesis and activated lipolysis, i.e., influenced the lipid metabolism of black sea bream.
    Matched MeSH terms: Isocitrate Dehydrogenase/analysis
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