Ý Nghĩa Lâm Sàng của Tâm Lý Học Phân Tử và Các Dấu Ấn Sinh Học đối với Glioma Ác Tính

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Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003. Gilbert MR, Wang M, Aldape KD, et al. RTOG 0525: A randomized phase III trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM). ASCO Meeting Abstracts. 2011;29:2006. • Reifenberger G, Hentschel B, Felsberg J et al. Predictive impact of MGMT promoter methylation in glioblastoma of the elderly. Int J Canc. Journal international du cancer 2011. This study indicates a predictive role of MGMT methylation in elderly patients with glioblastomas. Currently, the role of MGMT in this glioblastoma patient population is further characterized in randomized clinical trials. • Felsberg J, Thon N, Eigenbrod S et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Canc. Journal international du cancer 2011; 129: 659–670. This study demonstrates that the MGMT status is preserved in recurrent glioblastomas. McLendon R, Friedman A, Bigner D et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455: 1061–8. • Yip S, Miao J, Cahill DP et al. MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res. 2009; 15: 4622–9. Overcoming resistance to temozolomide therapy is a critical question. This study defines a role for the mismatch repair gene MSH6. Wick W, Hartmann C, Engel C, et al. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. 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This is a very important study demonstrating a connection between metabolics and epigenetics (ie, linking the presence of IDH mutations with hypermethylation). Prensner JR, Chinnaiyan AM. Metabolism unhinged: IDH mutations in cancer. Nat Med. 2011;17:291–3. Capper D, Simon M, Langhans CD et al. 2-Hydroxyglutarate concentration in serum from patients with gliomas does not correlate with IDH1/2 mutation status or tumor size. Int J Canc. Journal international du cancer 2011. Pope WB, Prins RM, Albert Thomas M et al. Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neuro Oncol 2011. Capper D, Weissert S, Balss J, et al. Characterization of R132H mutation-specific IDH1 antibody binding in brain tumors. Brain Pathol. 2010;20:245–54. Hartmann C, Hentschel B, Wick W, et al. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas. Acta Neuropathol. 2010;120:707–18. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73. •• Sanson M, Marie Y, Paris S et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol. 2009; 27: 4150–4. This is a very important study indicating that IDH1 codon 132 mutation is closely linked to the genomic profile of the tumor and constitutes an important prognostic marker in gliomas of different WHO grades. Dubbink HJ, Taal W, van Marion R, et al. IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide. Neurology. 2009;73:1792–5. Taal W, Dubbink HJ, Zonnenberg CB, et al. 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