Prevalence of IDH1/2 Mutations in Different Subtypes of Glioma in the North-East Population of Morocco

  • Senhaji, Nadia (Laboratory of Bioactive Molecules: Structure and Functions, Faculty of Science and Technology of Fez) ;
  • Louati, Sara (Laboratory of Bioactive Molecules: Structure and Functions, Faculty of Science and Technology of Fez) ;
  • Chbani, Laila (Pathological anatomy and molecular pathology Service. University Hospital Hassan II of Fez) ;
  • Bardai, Sanae El (Pathological anatomy and molecular pathology Service. University Hospital Hassan II of Fez) ;
  • Mikou, Karima (Laboratory of Bioactive Molecules: Structure and Functions, Faculty of Science and Technology of Fez) ;
  • MAAROUFI, Mustafa (Department of Radiology, University Hospital Hassan II of Fez) ;
  • Benzagmout, Mohammed (Department of Neurosurgery, University Hospital Hassan II of Fez) ;
  • Faiz, Mohammed Chaoui El (Department of Neurosurgery, University Hospital Hassan II of Fez) ;
  • Marie, Yannick (Institut du Cerveau et de la Moelle epiniere, ICM) ;
  • Mokhtari, Karima (Inserm, U 1127) ;
  • Idbaih, Ahmed (Inserm, U 1127) ;
  • Amarti, Afaf (Pathological anatomy and molecular pathology Service. University Hospital Hassan II of Fez) ;
  • Bennis, Sanae (Pathological anatomy and molecular pathology Service. University Hospital Hassan II of Fez)
  • 발행 : 2016.05.01


Background: Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. Materials and Methods: IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. Results: The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. Conclusions: Our results confirmed other studies published earlier for other populations with some small discrepancies.


  1. Agnihotri S, Aldape KD, Zadeh G (2014). Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma. Neurosurg Focus, 37, 13.
  2. Bleeker FE, Atai NA, Lamba S, et al (2010). The prognostic IDH1 (R132) mutation is associated with reduced NADP+2dependent IDH activity in glioblastoma. Acta Neuropathol, 119, 487-94.
  3. Camelo-Piragua S, Jansen M, Ganguly A, et al (2010). Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis. Acta Neuropathol, 119, 509-11.
  4. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, et al (2015). Comprehensive, integrative genomic analysis of diffuse lower grade-gliomas. N Engl J Med, 372, 2481-98.
  5. Capper D, Reuss D, Schittenhelm J, et al (2011). Mutation-specific IDH1 antibody differentiates oligodendrogliomas and oligoastrocytomas from other brain tumors with oligodendroglioma- like morphology. Acta Neuropathol, 121, 241-52.
  6. Capper D, Weissert S, Balss J, et al (2010). Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol, 20, 245-54.
  7. Capper D, Zentgraf H, Balss J, Hartmann C, von Deimling A (2009). Monoclonal antibody specific for IDH1 R132H mutation. Acta Neuropathol, 118, 599-01.
  8. Chen JR, Yao Y, Xu HZ, Qin ZY (2016). Isocitrate dehydrogenase (idh)1/2 mutations as prognostic markers in patients with glioblastomas. Medicine (Baltimore), 95, 2583.
  9. Christensen BC, Smith AA, Zheng S, et al (2011). DNA methylation, isocitrate dehydrogenase mutation, and survival in glioma. J Natl Cancer Inst, 103, 143-53.
  10. Clark O, Yen K, Mellinghoff IK (2016). Molecular pathways: isocitrate dehydrogenase mutations in cancer. Clin Cancer Res, 22, 1837-42.
  11. Davis M, Pragani R, Popovici-Muller J, et al (2013). ML309: a potent inhibitor of R132H mutant IDH1 capable of reducing 2-hydroxyglutarate production in U87 MG glioblastoma cells. Probe Reports from the NIH Molecular Libraries Program.
  12. Eckel-Passow JE, Lachance DH, Molinaro AM, et al (2015). Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med, 372, 2499-508.
  13. Gravendeel LA, Kouwenhoven MC, Gevaert O, et al (2009). Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology. Cancer Res, 69, 9065-72
  14. Hartmann C, Meyer J, Balss J, et al (2009). Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas. Acta Neuropathol, 118, 469-74.
  15. Hilmani S, Abidi O, Benrahma H, et al (2013). Clinicopathological features and molecular analysis of primary glioblastomas in Moroccan patients. Mol Neurosci, 49, 567-73.
  16. Houillier C, Wang X, Kaloshi G, et al (2010). IDH1 or IDH2 mutations predict longer survival and response to temozolomide in low-grade gliomas. Neurol, 75, 1560-66.
  17. Juratli TA, Cahill DP, McCutcheon IE (2015). Determining optimal treatment strategy for diffuse glioma: the emerging role of IDH mutations. Expert Rev Anticancer Ther, 15, 603-6.
  18. Killela PJ, Pirozzi CJ, Healy P, et al (2014). Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget, 5, 1515-25.
  19. Lee S M, Koh H J, Park DC, et al (2002). Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells. Free Radic Biol Med, 32, 1185-96.
  20. Leeper HE, Caron AA, Decker PA, et al (2015). IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas. Oncotarget, 6, 30295-305.
  21. Leu S, von Felten S, Frank S, Boulay JL, Mariani L (2016). IDH mutation is associated with higher risk of malignant transformation in low-grade glioma. J Neurooncol, 127, 363-72.
  22. Li S, Yan C, Huang L, et al (2012). Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China. Neuro Oncol, 14, 109-16.
  23. Louis D N, Ohgaki H, Wiestler OD, Cavenee WK (2007). WHO classification of tumors of the central nervous systems (4th edition). Lyon: International agency for research on cancer (IARC).
  24. Lv S, Teugels E, Sadones J, et al (2011). Correlation between IDH1 gene mutation status and survival of patients treated for recurrent glioma. Anticancer Res, 31, 4457-63.
  25. Mellai M, Piazzi A, Caldera V, et al (2011). IDH1 and IDH2 mutations, immunohistochemistry and associations in a series of brain tumors. J Neurooncol, 105, 345-57.
  26. Mukasa A, Takayanagi S, Saito K, et al (2012). Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients. Cancer Sci, 103, 587-92
  27. Nobusawa S, Watanabe T, Kleihues P, Ohgaki H (2009). IDH1 mutations as molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res, 15, 6002-7.
  28. Parsons D W, Jones S, Zhang X, et al (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321, 1807-12.
  29. Patel KP, Ravandi F, Ma D, et al (2011). Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am J ClinPathol, 135, 35-45.
  30. Pellegatta S, Valletta L, Corbetta C, et al (2015). Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma. Acta Neuropathol Commun, 3, 4.
  31. Pessoa IA, Sagica FE, Anselmo NP, Brito JR, de Oliveira EH (2015). IDH1 and IDH2 mutations in different histologic subtypes and WHO grading gliomas in a sample from Northern Brazil. Genet Mol Res, 14, 6533-42.
  32. Rohle D, Popovici-Muller J, Palaskas N et al. (2013). An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science, 340, 626-30.
  33. Sanson M, Marie Y, Paris S, et al (2009). Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol, 27, 4150-4.
  34. Schumacher T, Bunse L, Pusch S, et al (2014). A vaccine targeting mutant IDH1 induces antitumour immunity. Nature, 512, 324-7.
  35. Shibahara I, Sonoda Y, Kanamori M, et al (2012). IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas. Int J Clin Oncol, 17, 551-61.
  36. Van den Bent MJ, Dubbink HJ, Marie Y, et al (2010). IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the european organization for research and treatment of cancer brain tumor group. Clin Cancer Res, 16, 1597-604.
  37. Waitkus MS, Diplas BH, Yan H (2016). Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol, 18, 16-26.
  38. 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, 1149-53.
  39. Weller M, Felsberg J, Hartmann C, et al (2009). Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the german glioma network. J Clin Oncol, 27, 5743-50.
  40. Wick W, Hartmann C, Engel C, et al (2009). NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol, 27, 5874-80.
  41. Xia L, Wu B, Fu Z, et al (2015). Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational studies. Oncotarget, 6, 17354-65.
  42. Yan H, Parsons DW, Jin G, et al (2009). IDH1 and IDH2 mutations in gliomas. N Engl J Med, 360, 765-73.
  43. Zhang C-B, Bao Z-S, Wang H-J, et al (2014). Correlation of IDH1/2 mutation with clinicopathologic factors and prognosis in anaplastic gliomas: a report of 203 patients from China. J Cancer Res Clin Oncol, 140, 45-51.
  44. Zhang RQ, Shi Z, Chen H, et al (2016). Biomarker-based prognostic stratification of young adult glioblastoma. Oncotarget, 7, 5030-41.