Abstract
The objective of this study is to investigate the expression and significance of isocitrate dehydrogenase 1 (IDH1) mutation in different subtypes of human gliomas. Direct DNA sequencing, western blot, and immunohistochemistry were used to detect IDH1 mutation and IDH1 gene expression levels in 97 cases of glioma and 9 cases of other CNS tumors. IDH1 mutation was heterozygous, with wild-type arginine 132 replaced by histidine (R132H). Expression in different glioma subtypes was (1) 0 out if 5 in pilocytic astrocytoma; (2) 15 out of 22 in diffuse astrocytoma, 6 out of 9 in oligodendroglioma, 4 out of 6 in oligoastrocytoma, and 0 out of 4 in ependymoma; (3) 11 out of 19 in anaplastic astrocytoma, 4 out of 7 in anaplastic oligodendroglioma, 3 out of 4 in anaplastic oligoastrocytoma, and 0 out of 3 in anaplastic ependymoma; and (4) 1 out of 6 in primary glioblastoma, 8 out of 10 in secondary glioblastoma, and 0 out of 2 in medulloblastoma. IDH1 mutation is a somatic mutation that is found only in some glioma subtypes. It can be used as a molecular marker for glioma subtypes. For example, it can be used to distinguish primary glioblastoma from secondary glioblastoma, combining TP53 mutation and loss of heterozygosity involving 1p/19q. It can also be used as a marker for some gliomas. For example, it can be used to distinguish pilocytic astrocytoma from diffuse astrocytoma, combining detected BRAF proto-oncogene mutations.
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References
Aghili M, Zahedi F, Rafiee E (2009) Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review. J Neurooncol 91(2):233–236
DeBerardinis R, Lum J, Hatzivassiliou G, Thompson B (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7(1):11–20
Forshew T, Tatevossian RG, Lawson AR (2009) Activation of the ERK/MAPK pathway: a signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 218(2):172–181
Ichimura K, Bolin MB, Goike HM, Schmidt EE, Moshref A, Collins VP (2000) Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res 60(2):417–424
Kang MR, Kim MS, Oh JE et al (2009) Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers. Int J Cancer 125(2):353–355
Kil IS, Kim SY, Lee SJ, Park JW (2007) Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. Free Radic Biol Med 43(8):1197–1207
Kim SY, Lee SM, Tak JK, Choi KS, Kwon TK, Park JW (2007) Regulation of singlet oxygen-induced apoptosis by cytosolic NADP+-dependent isocitrate dehydrogenase. Mol Cell Biochem 302(1–2):27–34
Lee SM, Koh HJ, Park DC, Song BJ, Huh TL, Park JW (2002) Cytosolic NADP (+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radic Biol Med 32(11):1186–1186
Louis D, Ohgaki H, Wiesler O, Cavenee W (2007) WHO classification of tumours of the central nervous system. International Agency for Research on Cancer (IARC), Lyon
Ohgaki H, Kleihues P (2005) Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64(6):479–489
Ohgaki H, Kleihues P (2007) Genetic pathways to primary and secondary glioblastoma. Am J Pathol 170(5):1445–1453
Okamoto Y, Di Patre PL, Burkhard C et al (2004) Population-based study on incidence, survival rates, and genetic alterations of low-grade astrocytomas and oligodendrogliomas. Acta Neuropathol 108(1):49–56
Parsons D, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science 321(5897):1807–1812
Watanabe T, Nobusawa S, Kleihues P, Ohgaki H (2009) IDH1 mutations are early events in the development of astrocytomas and oligodendrogliomas. Am J Pathol 174(4):1149–1153
Xu X, Zhao J, Xu Z et al (2004) Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity. J Biol Chem 279(32):33946–33957
Yan H, Parsons DW, Jin G et al (2009) IDH1 and IDH2 mutations in gliomas. N Engl J Med 360(8):765–673
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This work was supported in part by the Major Issues Foundation of the Health Department of Jiangsu province (XK 20070022) and Suzhou Science and Technology Plan Projects (SYS201025).
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Zhou, YX., Wang, JX., Feng, M. et al. Analysis of Isocitrate Dehydrogenase 1 Mutation in 97 Patients with Glioma. J Mol Neurosci 47, 442–447 (2012). https://doi.org/10.1007/s12031-011-9681-5
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DOI: https://doi.org/10.1007/s12031-011-9681-5