Genetic and Epigenetic Factors Affecting Development and Prognosis of Brain Gliomas – a Review of Current Knowledge
Authors:
F. Kramář 1; M. Minárik 2,3; B. Belšánová 2; T. Hálková 2; O. Bradáč 1; D. Netuka 1; V. Beneš 1
Authors place of work:
Neurochirurgická a neuroonkologická klinika 1. LF UK a ÚVN – VFN Praha
1; Centrum aplikované genomiky solidních nádorů (CEGES), Genomac výzkumný ústav, s. r. o., Praha
2; Katedra analytické chemie, PřF UK v Praze
3
Published in the journal:
Cesk Slov Neurol N 2016; 79/112(4): 400-405
Category:
Review Article
doi:
https://doi.org/10.14735/amcsnn2016400
Summary
Gliomas represent a heterogenous group of primary brain tumors that can significantly vary in prognosis and treatment. The WHO Brain Tumors classification is based on morphological criteria that seem inadequate as they do not reflect new molecular markers. These new markers affect prognosis, overall survival and treatment more than histological diagnosis. IDH1/2 mutation and 1p/19q codeletion are the most important molecular markers predicting patient prognosis in lower grade gliomas and secondary glioblastomas. IDH1/2 mutation is a marker of better prognosis than wild type IDH. Similarly, ATRX plays an important role in anaplastic astrocytomas and loss of ATRX expression positively affects treatment response in these tumors. Clinical studies suggest that 1p/19q codeletion is the most relevant prognostic marker in oligodendroglial tumors, probably because of tumor chemosensitivity. Besides 1p/19q codeletion, TERT promoter mutation is another important factor in overall survival. Patients with gliomas carrying combined IDH1/2 mutation and 1p/19q codeletion have the best prognosis compared to those with wild type IDH. Glioblastomas are highly malignant glial tumors. Despite the progress in understanding of tumor formation and development, they are still difficult to treat. Nevertheless, MGMT promoter methylation in GBM is the most important predictor of good treatment response. A specific EGFRvIII mutation is another potential treatment target. Recently, single nucleotide polymorphisms (SNP) were found as another, in this case inherited, factor that can have an impact on a patient´s prognosis and treatment response. In particular, rs55705857 in anaplastic oligodendroglioma G allele carriers have much better prognosis in comparison to those who carry A allele. These new findings confirm that the prognosis is affected by multiple factors, including inherited predisposition.
Key words:
glioma – diffuse astrocytoma – anaplastic astrocytoma – oligodendroglioma – anaplastic oligodendroglioma – glioblastoma – molecular markers – single nucleotide polymorphism
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Zdroje
1. Dubbink HJ, Atmodimedjo PN, Kros JM, et al. Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial. Neuro Oncol 2015;18(3):388– 400. doi: 10.1093/ neuonc/ nov182.
2. Siegal T. Clinical impact of molecular biomarkers in gliomas. J Clin Neurosci Off J Neurosurg Soc Australas 2015;22(3):437– 44. doi: 10.1016/ j.jocn.2014.10.004.
3. Ostrom QT, Gittleman H, Fulop J, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008– 2012. Neuro Oncol 2015;17(Suppl 4):iv1– 62. doi: 10.1093/ neuonc/ nov189.
4. Verhaak RG, Hoadley KA, Purdom E, et al. An integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR and NF1. Cancer Cell 2010;17(1):98. doi: 10.1016/ j.ccr.2009.12.020.
5. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462(7274):739. doi: 10.1038/ nature08617.
6. Cohen AL, Holmen SL, Colman H. IDH1 and IDH2 mutations in gliomas. Curr Neurol Neurosci Rep 2013;13(5):345. doi: 10.1007/ s11910-013-0345-4.
7. Schiff D, Purow B. Neuro-oncology: five new things. Neurol Clin Pract 2013;3(4):326– 33. doi: 10.1212/ CPJ.0b013e3182a1ba35.
8. Megova M, Drabek J, Koudelakova V, et al. Isocitrate dehydrogenase 1 and 2 mutations in gliomas. J Neurosci Res 2014;92(12):1611– 20. doi: 10.1002/ jnr.23456.
9. Seltzer MJ, Bennett BD, Joshi AD, et al. Inhibition of glutaminase preferentially slows growth of glioma cellswith mutant IDH1. Cancer Res 2010;70(22):8981– 7. doi: 10.1158/ 0008-5472.CAN-10-1666.
10. Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 2012;483(7390):474– 8. doi: 10.1038/ nature10860.
11. Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 2012;483(7390):479– 83. doi: 10.1038/ nature10866.
12. Noushmehr H, Weisenberger DJ, Diefes K, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 2010;17(5):510– 22. doi: 10.1016/ j.ccr.2010.03.017.
13. Camelo-Piragua S, Jansen M, Ganguly A, et al. Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from astrocytosis. Acta Neuropathol (Berl) 2010;119(4):509– 11. doi: 10.1007/ s00401-009-0632-y.
14. Li L, Paz AC, Wilky BA, et al. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells. PloS One 2015;10(9):e0133813. doi: 10.1371/ journal.pone.0133813.
15. Suijker J, Oosting J, Koornneef A, et al. Inhibition of mutant IDH1 decreases D-2-HG levels without affecting tumorigenic properties of chondrosarcoma cell lines. Oncotarget 2015;6(14):12505– 19.
16. Kernytsky A, Wang F, Hansen E, et al. IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition. Blood 2015;125(2):296– 303. doi: 10.1182/ blood-2013-10-533604.
17. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific Genetic Predictors of Chemotherapeutic Response and Survival in Patients With Anaplastic Oligodendrogliomas. J Natl Cancer Inst 1998;90(19):1473– 9.
18. Cairncross G, Wang M, Shaw E, et al. Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402. J Clin Oncol 2013;31(3):337– 43. doi: 10.1200/ JCO.2012.43.2674.
19. Cairncross JG, Wang M, Jenkins RB, et al. Benefit From Procarbazine, Lomustine, and Vincristinein Oligodendroglial Tumors Is Associated With Mutationof IDH. J Clin Oncol 2014;32(8):783– 90. doi: 10.1200/ JCO. 2013.49.3726.
20. Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med 2015;372(26):2481– 98. doi: 10.1056/ NEJMoa1402121.
21. Killela PJ, Reitman ZJ, Jiao Y, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci U S A 2013;110(15):6021– 6. doi: 10.1073/ pnas.1303607110.
22. Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma Groups Based on 1p/ 19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med 2015;372(26): 2499– 508. doi: 10.1056/ NEJMoa1407279.
23. Reuss DE, Sahm F, Schrimpf D, et al. ATRX and IDH1-R132H immunohistochemistry with subsequent copy number analysis and IDH sequencing as a basis for an “integrated” diagnostic approach for adult astrocytoma, oligodendroglioma and glioblastoma. Acta Neuropathol (Berl) 2015;129(1):133– 46. doi: 10.1007/ s00401-014-1370-3.
24. Kannan K, Inagaki A, Silber J, et al. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 2012;3(10):1194– 203.
25. Wiestler B, Capper D, Holland-Letz T, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol (Berl) 2013;126(3):443– 51. doi: 10.1007/ s00401-013-1156-z.
26. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. N Engl J Med 2005;352(10):987– 96. doi: 10.1056/ NEJMoa043330.
27. Hegi ME, Diserens AC, Gorlia T, et al. MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma. N Engl J Med 2005;352(10):997– 1003. doi: 10.1056/ NEJMoa043331.
28. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008;455(7216):1061– 8. doi: 10.1038/ nature07385.
29. Zussman BM, Engh JA. Outcomes of the ACT III Study: Rindopepimut (CDX-110) Therapy for Glioblastoma. Neurosurgery 2015;76(6):N17. doi: 10.1227/ 01.neu.0000465855.63458.0c.
30. Jenkins RB, Xiao Y, Sicotte H, et al. A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation. Nat Genet 2012;44(10):1122– 5. doi: 10.1038/ ng.2388.
31. Fogli A, Chautard E, Vaurs-Barrière C, et al. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients’ survival. Carcinogenesis 2015;37(2):169– 76. doi: 10.1093/ carcin/ bgv251.
32. Rapkins RW, Wang F, Nguyen HN, et al. The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide. Neuro Oncol 2015;17(12):1589– 98. doi: 10.1093/ neuonc/ nov064.
33. Shete S, Hosking FJ, Robertson LB, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 2009;41(8):899– 904. doi: 10.1038/ ng.407.
34. Sanson M, Hosking FJ, Shete S, et al. Chromosome 7p11.2 (EGFR) variation influences glioma risk. HumMol Genet 2011;20(14):2897– 904. doi: 10.1093/ hmg/ ddr192.
35. Kramar F, Zemanova Z, Michalova K, et al. Cytogenetic analyses in 81 patients with brain gliomas: correlation with clinical outcome and morphological data. J Neurooncol 2007;84(2):201– 11. doi: 10.1007/ s11060-007-9358-7.
36. Brennan CW, Verhaak RGW, McKenna A, et al. The somatic genomic landscape of glioblastoma. Cell 2013;155(2):462– 77. doi: 10.1016/ j.cell.2013.09.034.
37. Mao H, LeBrun DG, Yang J, et al. Deregulated Signaling Pathways in Glioblastoma Multiforme: Molecular Mechanisms and Therapeutic Targets. Cancer Invest 2012;30(1):48– 56. doi: 10.3109/ 07357907.2011.630050.
38. Kalita O, Kramář F, Neumann E, et al. Současný stav léčby anaplastických gliomů v České republice. Cesk Slov Neurol N 2015;78/ 111(3):306– 16.
Štítky
Paediatric neurology Neurosurgery NeurologyČlánok vyšiel v časopise
Czech and Slovak Neurology and Neurosurgery
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