Malignant astrocytomas of elderly patients lack favorable molecular markers: an analysis of the NOA-08 study collective
The number of patients age >65 years with malignant gliomas is increasing. Prognosis of these patients is worse compared with younger patients. To determine biological differences among malignant gliomas of different age groups and help to explain the survival heterogeneity seen in the NOA-08 tri...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 17, 2013
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| In: |
Neuro-Oncology
Year: 2013, Volume: 15, Issue: 8, Pages: 1017-1026 |
| ISSN: | 1523-5866 |
| DOI: | 10.1093/neuonc/not043 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/neuonc/not043
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| Author Notes: | Benedikt Wiestler, Rainer Claus, Sabine A. Hartlieb, Maximilian G. Schliesser, Elisa K. Weiss, Thomas Hielscher, Michael Platten, Laura M. Dittmann, Christoph Meisner, Jörg Felsberg, Caroline Happold, Matthias Simon, Guido Nikkhah, Kirsten Papsdorf, Joachim P. Steinbach, Michael Sabel, Christiane Grimm, Dieter Weichenhan, Björn Tews, Guido Reifenberger, David Capper, Wolf Müller, Christoph Plass, Michael Weller, and Wolfgang Wick, for the Neuro-oncology Working Group (NOA) of the German Cancer Society |
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| 245 | 1 | 0 | |a Malignant astrocytomas of elderly patients lack favorable molecular markers |b an analysis of the NOA-08 study collective |c Benedikt Wiestler, Rainer Claus, Sabine A. Hartlieb, Maximilian G. Schliesser, Elisa K. Weiss, Thomas Hielscher, Michael Platten, Laura M. Dittmann, Christoph Meisner, Jörg Felsberg, Caroline Happold, Matthias Simon, Guido Nikkhah, Kirsten Papsdorf, Joachim P. Steinbach, Michael Sabel, Christiane Grimm, Dieter Weichenhan, Björn Tews, Guido Reifenberger, David Capper, Wolf Müller, Christoph Plass, Michael Weller, and Wolfgang Wick, for the Neuro-oncology Working Group (NOA) of the German Cancer Society |
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| 520 | |a The number of patients age >65 years with malignant gliomas is increasing. Prognosis of these patients is worse compared with younger patients. To determine biological differences among malignant gliomas of different age groups and help to explain the survival heterogeneity seen in the NOA-08 trial, the prevalence and impact of recently established biomarkers for outcome in younger patients were characterized in elderly patients.Prevalences of mutations of isocitrate dehydrogenase 1 (IDH1) and histone H3.3 (H3F3A), the glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and methylation of alkylpurine DNA N-glycosylase (APNG) and peroxiredoxin 1 (PRDX1) promoters were determined in a representative biomarker subset (n = 126 patients with anaplastic astrocytoma or glioblastoma) from the NOA-08 trial.IDH1 mutations (R132H) were detected in only 3/126 patients, precluding determination of an association between IDH mutation and outcome. These 3 patients also displayed the G-CIMP phenotype. None of the IDH1 wild-type tumors were G-CIMP positive. Mutations in H3F3A were absent in all 103 patients sequenced for H3F3A. MassARRAY analysis of the APNG promoter revealed generally low methylation levels and failed to confirm any predictive properties for benefit from alkylating chemotherapy. Neither did PRDX1 promoter methylation show differential methylation or association with outcome in this cohort. In a 170-patient cohort from The Cancer Genome Atlas database matched for relevant prognostic factors, age ≥65 years was strongly associated with shorter survival.Despite an age-independent stable frequency of O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation, tumors in this age group largely lack prognostically favorable markers established in younger glioblastoma patients, which likely contributes to the overall worse prognosis of elderly patients. However, the survival differences hint at fundamental further differences among malignant gliomas of different age groups. | ||
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