The relationship between IDH, P53 mutations, MGMT methylation with characteristics in high grade glioma patients
Keywords:
mutant IDH, mutant TP53, MGMT methylation, high grade glioma.Abstract
Introduction: Some gene mutations in high grade glioma patients have many implications in prognosis and treatment response.Objectives: To describe the characteristics and associations of IDH, TP53 gene mutations and MGMT methylation status with some characteristics and treatment response in patients with high grade glioma.
Methods: A descriptive, prospective, uncontrolled study was conducted, in 52 patients with high-grade glioma. Research variables include age, sex, Karnofsky score, the rate of IDH, P53 mutation, MGMT methylation; the relationship between genes mutation with some characteristics and response to treatment according to the RECIST classification.
Results: For IDH gene mutation, grade III patients (23.1%) have a higher positive rate than grade IV (11.5 %); for P53 gene mutation, grade III patients (55.6 %) have a higher positive rate than grade IV (44.1 %); the rate of MGMT promoter methylation occurred in the study group of patients with the rate of 42.3 %. There is a relationship between IDH gene mutation with pathological results and malignancy in studied patients. Patients with the mutant expression of the IDH gene, p53, MGMT methylation status had better RECIST responses than patients without these expressions.
Conclusion: High-grade glioma mainly occurs in men, over 40 years old. The presence of mutations in IDH, P53 genes, and MGMT methylation status was a beneficial factor for treatment response as assessed by RECIST.
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References
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22. Friedman HS, McLendon RE, Kerby T, Dugan M, Bigner SH, Henry AJ, et al. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol. 1998 [access: 01/12/1998]; 16(12):3851-7. Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.1998.16.12.3851
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24. Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 [access: 01/09/2014]; 25 (Suppl 3):iii93-101. Available at: https://www.annalsofoncology.org/article/S0923-7534(19)34077-3/fulltext
2. Burnet NG, Jefferies SJ, Benson RJ, Hunt DP, Treasure FP. Years of life lost (YLL) from cancer is an important measure of population burden—and should be considered when allocating research funds. British Journal of Cancer. 2005 [access: 06/12/2016]; 92: 241-5. Available at: https://www.nature.com/articles/6602321
3. Stupp R, Warren PM, Martin JB, Weller M, Barbara F, Martin JBT, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal Medicine. 2005 [access: 06/12/2016]; 352(10): 987-96. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa043330
4. Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, et al. Malignant glioma: genetics and biology of a grave matter. Genes & Development. 2001 [access: 01/06/2001]; 15(11): 1311-33. Available at: http://genesdev.cshlp.org/content/15/11/1311.long
5. Ollivier L, Padhani AR. The RECIST criteria: implications for diagnostic radiologists. The British Journal of Radiology. 2001 [access: 14/05/2001]; 74(887): 983–6. Available at: http://recist.com.br/PDF/Artigo%20RECIST.pdf
6. Rasmussen BK, Hansen S, Laursen RJ, Kosteljanetz M, Schultz H, Nørgård BM, et al. Epidemiology of glioma: clinical characteristics, symptoms, and predictors of glioma patients grade I–IV in the the Danish Neuro-Oncology Registry. Journal of Neuro-Oncology. 2017 [access: 31/08/2017]; 135(3):571–9. Available at: https://pubmed.ncbi.nlm.nih.gov/28861666/
7. Hoffman S, Propp JM, McCarthy BJ. Temporal trends in incidence of primary brain tumors in the United States, 1985-1999. Neuro Oncol. 2006 [access: 01/01/2006]; 8(1):27-37. Available at: https://pubmed.ncbi.nlm.nih.gov/16443945/
8. Ho J, Ondos J, Ning H, Smith S, Kreisl T, Iwamoto F, et al. Chemoirradiation for Glioblastoma Multiforme: The National Cancer Institute Experience. PLoS ONE. 2013 [access: 05/08/2013]; 8(8): e70745. Available at: https://pubmed.ncbi.nlm.nih.gov/23940635/
9. Ichimura K, Pearson DM, Kocialkowski S, Bäcklund LM, Chan R, Jones DT, et al. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas. Neuro Oncol. 2009 [access: 01/08/2009]; 11(4): 341-7. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743214/
10. Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta Neuropathol. 2008 [access: 05/12/2008]; 116(6): 597-602. Available at: https://pubmed.ncbi.nlm.nih.gov/18985363/
11. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. New England Journal of Medicine. 2009 [access: 19/02/2009]; 360(8): 765-73. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820383/
12. Turkalp Z, Karamchandani J, Das S. IDH mutation in glioma: new insights and promises for the future. JAMA Neurol. 2014 [access: 25/08/2014]; 71(10):1319-25. Available at: https://jamanetwork.com/journals/jamaneurology/fullarticle/1897092
13. Cairncross JG, Wang M, Jenkins RB, Shaw EG, Giannini C, Brachman DG, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol. 2014 [access: 10/03/2014]; 32(8):783-90. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940537/
14. Tada M, Iggo RD, Waridel F, Nozaki M, Matsumoto R, Sawamura Y, et al. Reappraisal of p53 mutations in human malignant astrocytic neoplasms by p53 functional assay: comparison with conventional structural analyses. Molecular Carcinogenesis. 1997 [access: 01/03/1997]; 18(3):171-6. Available at: https://pubmed.ncbi.nlm.nih.gov/9115587/
15. Baker SJ. Redefining p53 – entering the tumor suppressor era. Cell Cycle. 2003 [access: 01/01/2003]; 2(1):7-8. Available at: https://www.tandfonline.com/doi/pdf/10.4161/cc.2.1.288
16. Faria MH, Neves Filho EH, Alves MK, Burbano RM, de Moraes Filho MO, Rabenhorst SH. TP53 mutations in astrocytic gliomas: an association with histological grade, TP53 codon 72 polymorphism and p53 expression. APMIS. 2012; 120(11):882-9. DOI: 10.1111/j.1600-0463.2012.02918.x
17. Watanabe K, Sato K, Biernat W, Tachibana O, von Ammon K, Ogata N, et al. Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clinical Cancer Research. 1997 [access: 01/03/1997]; 3(4):523-30. Available at: https://aacrjournals.org/clincancerres/article/3/4/523/8205/Incidence-and-timing-of-p53-mutations-during
18. Zawlik I, Kita D, Vaccarella S, Mittelbronn M, Franceschi S, Ohgaki H. Common polymorphisms in the MDM2 and TP53 genes and the relationship between TP53 mutations and patient outcomes in glioblastomas. Brain Pathol. 2009 [access: 01/03/2009]; 19(2):188-94. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094731/
19. Barnholtz-Sloan J, Sloan AE, Land S, Kupsky W, Monteiro AN. Somatic alterations in brain tumors. Oncol Rep. 2008 [access: 01/07/2008]; 20(1):203-10. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933973/
20. Blough MD, Beauchamp DC, Westgate MR, Kelly JJ, Cairncross JG. Effect of aberrant p53 function on temozolomide sensitivity of glioma cell lines and brain tumor initiating cells from glioblastoma. J Neurooncol. 2011 [access: 01/03/2011]; 102(1):1-7. Available at: https://link.springer.com/article/10.1007/s11060-010-0283-9
21. Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine? Nat Rev Neurol. 2010 [access: 01/01/2010]; 6(1):39-51. Available at: https://www.nature.com/articles/nrneurol.2009.197
22. Friedman HS, McLendon RE, Kerby T, Dugan M, Bigner SH, Henry AJ, et al. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol. 1998 [access: 01/12/1998]; 16(12):3851-7. Available at: https://ascopubs.org/doi/pdf/10.1200/JCO.1998.16.12.3851
23. Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014 [access: 01/08/2014]; 15(9):e395-403. Available at: https://www.zora.uzh.ch/id/eprint/98103/
24. Stupp R, Brada M, van den Bent MJ, Tonn JC, Pentheroudakis G. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 [access: 01/09/2014]; 25 (Suppl 3):iii93-101. Available at: https://www.annalsofoncology.org/article/S0923-7534(19)34077-3/fulltext
Published
2022-07-15
How to Cite
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Tran DA, Nguyen BV, Nguyen BT, Vu HV, Nguyen LD. The relationship between IDH, P53 mutations, MGMT methylation with characteristics in high grade glioma patients. Rev Cubana Med Milit [Internet]. 2022 Jul. 15 [cited 2025 Apr. 18];51(3):e02202004. Available from: https://revmedmilitar.sld.cu/index.php/mil/article/view/2004
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