Abstract
Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, −9p, and −11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.
Highlights
Gliomas are currently classified according to their histological appearance, and the associated malignancy is defined by the World Health Organization (WHO) grading system
The histological diagnosis of the 237 adult supratentorial gliomas evaluated in this study included astrocytomas, oligodendrogliomas, oligoastrocytomas, and glioblastomas; isocitrate dehydrogenase 1 (IDH1)/2 and TP53 mutation statuses were determined via direct sequencing (S1 Fig)
IDH mutant gliomas with TP53 mutations and IDH wild-type gliomas were both associated with high recurrence rates, the median progression-free survival (PFS) in the latter group was significantly shorter than that in the former group (Table 1B and Fig 1C; hazard ratio = 0.229; 95% confidence interval [CI]: 0.142–0.368; p < 0.0001)
Summary
Gliomas are currently classified according to their histological appearance, and the associated malignancy is defined by the World Health Organization (WHO) grading system. We previously reported that adult supratentorial gliomas could be classified into genetic subgroups on the basis of their copy number aberrations (CNAs) using comparative genomic hybridization (CGH) and suggested that gliomas with +7q and 1p/ 19q co-deletions may have a better prognosis than those with −9p, −10q, and +7 CNAs [1]. The clinical significance of isocitrate dehydrogenase 1 (IDH1) point mutation in gliomas was first reported in 2008, the overall survival (OS) of glioblastoma patients with IDH1mutated glioblastoma was demonstrated to be significantly longer than that of patients with wild-type IDH1 glioblastoma [2]. The data demonstrated that IDH1 mutant gliomas with −1p/19q and +7q CNAs are associated with a better prognosis than that associated with IDH1 wild-type gliomas
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