Browse > Article
http://dx.doi.org/10.7314/APJCP.2013.14.12.7261

Molecular Investigation of Isocitrate Dehydrogenase Gene (IDH) Mutations in Gliomas: First Report of IDH2 Mutations in Indian Patients  

Ranjan Das, Bibhu (Research and Development, SRL Ltd.)
Tangri, Rajiv (SRL Ltd.)
Ahmad, Firoz (Research and Development, SRL Ltd.)
Roy, Arnab (Research and Development, SRL Ltd.)
Patole, Kamlakar (Histopathology Division, SRL Ltd.)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.12, 2013 , pp. 7261-7264 More about this Journal
Abstract
Recent genome wide sequencing has identified mutations in IDH1/IDH2 predominantly in grade II-III gliomas and secondary glioblastomas which are associated with favorable clinical outcome. These mutations have become molecular markers of significant diagnostic and prognostic relevance in the assessment of human gliomas. In the current study we evaluated IDH1 (R132) and IDH2 (R172) in 32 gliomas of various grades and tumor subtypes. Sequencing analysis revealed R132H mutations in 18.7% tumors, while none of the cases showed IDH2 (R172) mutations. The frequency of IDH1 mutations was higher in females (21.4%) than males (11.1%), and it was significantly higher in younger patients. Histological analyses demonstrated presence of necrosis and micro vascular proliferation in 69% and 75% respectively. Interestingly, IDH1 mutations were predominantly present in non-necrotic tumors as well as in cases showing microvascular proliferation. Of the six IDH1 positive cases, three were glioblastomas (IV), and one each were anaplastic oligoastrocytoma (III), anaplastic oligodendroglioma III (n=1) and diffuse astrocytoma. In conclusion, IDH1 mutations are quite frequent in Indian glioma patients while IDH2 mutations are not observed. Since IDH mutations are associated with good prognosis, their use in routine clinical practice will enable better risk stratification and management of glioma patients.
Keywords
Glioma; IDH1 mutation; IDH2 mutation; sequencing; India;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bleeker FE, Lamba S, Leenstra S, et al (2009). IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors. Hum Mutat, 30, 7-11.   DOI   ScienceOn
2 Burger PC, Scheithauer BW, Paulus W, et al (2000). Pilocytic astrocytoma. In: Kleihues P, Cavenee WK, eds. Pathology and Genetics of Tumours of the Nervous System. Lyon, France: IARC Press, 45-51.
3 Cykowski MD, Allen RA, Fung KM, et al (2012). Pyrosequencing of IDH1 and IDH2 mutations in brain tumors and nonneoplastic conditions. Diagn Mol Pathol, 21, 214-20.   DOI
4 Felsberg J, Wolter M, Seul H, et al (2010). Rapid and sensitive assessment of the IDH1 and IDH2 mutation status in cerebral gliomas based on DNA pyrosequencing. Acta Neuropathol, 119, 501-7.   DOI
5 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.   DOI   ScienceOn
6 Horbinski C, Kofler J, Kelly LM, et al (2009). Diagnostic use of IDH1/2 mutation analysis in routine clinical testing of formalin-fixed, paraffin-embedded glioma tissues. J Neuropathol Exp Neurol, 68, 1319-25.   DOI
7 Jha P, Suri V, Sharma V, et al (2011). IDH1 mutations in gliomas: first series from a tertiary care centre in India with comprehensive review of literature. Exp Mol Pathol, 91, 385-93.   DOI   ScienceOn
8 Jones DT, Kocialkowski S, Liu L, et al (2008). Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res, 68, 8673-7.   DOI   ScienceOn
9 Koivunen P, Lee S, Duncan CG, et al (2012). Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature, 483, 484-8.   DOI   ScienceOn
10 Krell D, Assoku M, Galloway M, et al (2011). Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH mutations in glioblastoma. PLoS One, 6, 19868.   DOI
11 Losman JA, Looper RE, Koivunen P, et al (2013). (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science, 339, 1621-5.   DOI   ScienceOn
12 Metellus P, Coulibaly B, Colin C, et al (2010). Absence of IDH mutation identifies a novel radiologic and molecular subtype of WHO grade II gliomas with dismal prognosis. Acta Neuropathol, 120, 719-29.   DOI   ScienceOn
13 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.   DOI   ScienceOn
14 Parsons DW, Jones S, Zhang X, et al (2008). An integrated genomic analysis of human glioblastoma multiforme. Science, 321, 1807-12.   DOI   ScienceOn
15 Qi ST, Yu L, Lu YT, et al (2011). IDH mutations occur frequently in Chinese glioma patients and predict longer survival but not response to concomitant chemoradiotherapy in anaplastic gliomas. Oncol Rep, 26, 1479-85.
16 Raynaud S, Carbuccia N, Colin C, et al (2010). Absence of R140Q mutation of isocitrate dehydrogenase 2 in gliomas and breast cancers. Oncol Lett, 1, 883-4.   DOI
17 Uno M, Oba-Shinjo SM, Silva Rd, et al (2011). IDH1 mutations in a Brazilian series of Glioblastoma. Clinics (Sao Paulo), 66, 163-5.   DOI   ScienceOn
18 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.   DOI   ScienceOn
19 Song Tao Q, Lei Y, Si G, et al (2012). IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci, 103, 269-73.   DOI   ScienceOn
20 Turcan S, Rohle D, Goenka A, et al (2012). IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature, 483, 479-83.   DOI   ScienceOn
21 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.   DOI
22 WickW, Hartmann C, Engel C, et al (2009). M. 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.   DOI   ScienceOn
23 Yan H, Parsons DW, Jin G, et al (2009). IDH1 and IDH2 mutations in gliomas. N Engl J Med, 360, 765-73.   DOI   ScienceOn
24 Zhu J, Zuo J, Xu Q, et al (2011). Isocitrate dehydrogenase mutations may be a protective mechanism in glioma patients. Med Hypotheses, 76, 602-3   DOI   ScienceOn