Skip to main content Skip to main navigation menu Skip to site footer

IDH1 mutation in Balinese glioma patients and its relationship with clinicopatological parameters

Abstract

Purpose: Isocitrate dehydrogenase 1 (IDH1) mutation plays an important role in the carcinogenesis of gliomas. The most recent WHO classification of central nervous system tumors has added molecular genetic in addition to the histological features of the tumor, including status of IDH mutation in glial tumors. The purpose of this study was to determine the prevalence of IDH1 mutations in Balinese glioma patients and its association with clinicopathological features.

Patients and methods: This study was conducted from 30 glioma patients at Sanglah General Hospital during January 2018 until June 2019. DNA extractions were carried out from the FFPE of tumor tissue, followed by amplification of codon 132 in exon 4 of the IDH1 gene by allele specific PCR. Relationship between IDH1 mutation status and clinicopathological features was tested with X2 with 0.05 significance.

Results: The age range of patients is 14-81 years with an average age of 43.4 years (SD±17.9 years). Most patients with astrocytic tumors (25/30; 83.3%), others were oligodendroglial tumor (2/30; 6.7%) and oligoastrocytic tumor (3/30; 10%). Most patients were found with grade IV glioblastoma (18/30; 60%).  Genotyping analysis showed IDH1 mutations in the majority of glioma patients (90%). Most cases (92.6%) of mutant IDH1 showed heterozygous mutations (GA genotype) while the rest showed homozygous mutations (AA genotype). There were no significant relationship between IDH1 status and age (p=0.09), sex (p=0.63) and histologic type (0.14), but there was significant relationship between IDH1 mutation status and tumor grade (p=0.01). All of IDH1 mutation were found in diffuse glioma (grade II and III gliomas and grade IV glioblastoma).

Conclusion: Most of diffuse glioma (grade II-IV glioma) patients in Bali had IDH1 mutation and IDH1 mutation status has significant relationship with tumor grade. Further research about genetic abnormalities in order to improve therapeutic efficacy against IDH-mutated gliomas is needed.

References

  1. Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803–820. doi:10.1007/s00401-016-1545-1
  2. Komori T. The 2016 WHO classification of tumours of the central nervous system: The major points of revision. Neurol Med Chir (Tokyo). 2017;57(7):301–311. doi:10.2176/nmc.ra.2017-0010
  3. Lee SC. Diffuse gliomas for nonneuropathologists: The new integrated molecular diagnostics. Arch Pathol Lab Med. 2018;142(7):804–814. doi:10.5858/arpa.2017-0449-RA
  4. Park SH, Won J, Kim SI, et al. Molecular testing of brain tumor. J Pathol Transl Med. 2017;51(3):205–223. doi:10.4132/jptm.2017.03.08
  5. Han S, Liu Y, Cai SJ, et al. IDH mutation in glioma: molecular mechanisms and potential therapeutic targets. Br J Cancer. 2020;122(11):1580–1589. doi:10.1038/s41416-020-0814-x
  6. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. Published online 2009. doi:10.1056/NEJMoa0808710
  7. Olar A, Wani KM, Alfaro-Munoz KD, et al. IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II–III diffuse gliomas. Acta Neuropathol. Published online 2015. doi:10.1007/s00401-015-1398-z
  8. Songtao Q, Lei Y, Si G, et al. IDH mutations predict longer survival and response to temozolomide in secondary glioblastoma. Cancer Sci. 2012;103(2):269–273. doi:10.1111/j.1349-7006.2011.02134.x
  9. Amankulor NM, Kim Y, Arora S, et al. Mutant idh1 regulates the tumor-associated immune system in gliomas. Genes Dev. 2017;31(8):774–786. doi:10.1101/gad.294991.116
  10. Loussouarn D, Le Loupp AG, Frenel JS, et al. Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas. Int J Oncol. 2012;40(6):2058–2062. doi:10.3892/ijo.2012.1404
  11. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science (80- ). 2008;321(5897):1807–1812. doi:10.1126/science.1164382
  12. Mukasa A, Takayanagi S, Saito K, et al. Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients. Cancer Sci. 2012;103(3):587–592. doi:10.1111/j.1349-7006.2011.02175.x
  13. Deng L, Xiong P, Luo Y, et al. Association between IDH1/2 mutations and brain glioma grade. Oncol Lett. 2018;16(4):5405–5409. doi:10.3892/ol.2018.9317
  14. Yusoff AAM, Zulfakhar FN, Sul’ain MD, Idris Z, Abdullah JM. Association of the IDH1 C.395G > A (R132H) mutation with histological type in malay brain tumors. Asian Pacific J Cancer Prev. 2016;17(12):6095–6101. doi:10.22034/APJCP.2016.17.12.6095

How to Cite

Sriwidyani, N. P., Wahyuniari, I. A. I., Saputra, H., & Arijana, I. G. K. N. (2020). IDH1 mutation in Balinese glioma patients and its relationship with clinicopatological parameters. Bali Medical Journal, 9(3), 819–822. https://doi.org/10.15562/bmj.v%vi%i.2077

HTML
0

Total
13

Share

Search Panel

Ni Putu Sriwidyani
Google Scholar
Pubmed
BMJ Journal


Ida Ayu Ika Wahyuniari
Google Scholar
Pubmed
BMJ Journal


Herman Saputra
Google Scholar
Pubmed
BMJ Journal


I Gusti Kamasan Nyoman Arijana
Google Scholar
Pubmed
BMJ Journal