Gliome: Molekulare Marker für die Therapieentscheidung – Kontra

Kontra

Maligne Gliome sind genetisch heterogen. Genetische Heterogenität korreliert zu unterschiedlicher Prognose [1]. Analysen auf verschiedenen molekularen Ebenen führen zu einer zunehmenden Untergruppierung früher einheitlicher Diagnosen wie des Glioblastoms [2] [3] und zu Vorhersagen möglicher Ansatzpunkte für Therapiestrategien [4].

• Literatur

• 1 Riemenschneider MJ, Louis DN, Weller M et al. Refined brain tumor diagnostics and stratified therapies: the requirement for a multidisciplinary approach. Acta Neuropathol 2013; 126: 21-37
• 2 Huse JT, Phillips HS, Brennan CW. Molecular subclassification of diffuse gliomas: seeing order in the chaos. Glia 2011; 59: 1190-1199
• 3 Sturm D, Witt H, Hovestadt V et al. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell 2012; 22: 425-437
• 4 Sturm D, Bender S, Jones DT et al. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer 2014; 14: 92-107
• 5 Weller M, Kaulich K, Hentschel B et al. Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy. Int J Cancer 2014; 134: 2437-2447
• 6 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: 337-343
• 7 van den Bent MJ, Brandes AA, Taphoorn MJ et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 2013; 31: 344-350
• 8 Idbaih A, Marie Y, Pierron G et al. Two types of chromosome 1p losses with opposite significance in gliomas. Ann Neurol 2005; 58: 483-487
• 9 Jha P, Sarkar C, Pathak P et al. Detection of allelic status of 1p and 19q by microsatellite-based PCR versus FISH: limitations and advantages in application to patient management. Diagn Mol Pathol 2011; 20: 40-47
• 10 Wiestler B, Capper D, Hovestadt V et al. Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial. Neuro Oncol 2014; 16: 1630-1638
• 11 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: 707-718
• 12 Stupp R, Mason WP, van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987-996
• 13 Malmstrom A, Gronberg BH, Marosi C et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 2012; 13: 916-926
• 14 Wick W, Platten M, Meisner C et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 2012; 13: 707-715
• 15 Cankovic M, Nikiforova MN, Snuderl M et al. The role of MGMT testing in clinical practice: a report of the association for molecular pathology. J Mol Diagn 2013; 15: 539-555
• 16 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
• 17 Armstrong TS, Wefel JS, Wang M et al. Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma. J Clin Oncol 2013; 31: 4076-4084
• 18 Chinot OL, de La Motte Rouge T, Moore N et al. AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. Adv Ther 2011; 28: 334-340
• 19 Idbaih A, Omuro A, Ducray F et al. Molecular genetic markers as predictors of response to chemotherapy in gliomas. Curr Opin Oncol 2007; 19: 606-611
• 20 Reifenberger G, Weber RG, Riehmer V et al. Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling. Int J Cancer 2014; 135: 1822-1831
• 21 Ducray F, Marie Y, Sanson M. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360: 2248-2249; author reply 2249
• 22 Schumacher T, Bunse L, Pusch S et al. A vaccine targeting mutant IDH1 induces antitumour immunity. Nature 2014; 512: 324-327
• 23 Rohle D, Popovici-Muller J, Palaskas N et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science 2013; 340: 626-630