Abstract
BackgroundAt current prognostication of low grade glioma remains suboptimal and might be improved with additional markers. These may guide treatment decisions, in particular on early adjuvant therapy versus wait and see after surgery.MethodsWe used a targeted Next-Generation Sequencing panel to assess mutational and copy number status of selected genes and chromosomes in a consecutive series of adult grade II supratentorial glioma, and assessed the impact of molecular markers of interest on overall survival.Results207 IDH mutated grade II glioma samples were analyzed with a median follow-up of 6.9 years. Loss of region 9p21.3 did not show a correlation with outcome in IDH mutated 1p/19q-codeleted oligodendroglioma or IDH mutated astrocytoma. We found a significant shorter overall survival with univariable analysis in IDH mutated astrocytoma patients with trisomy of chromosome 7 (Log rank P = 0.044) and in IDH mutated 1p/19q-codeleted oligodendroglioma patients with a PTEN mutation (Log rank P = 0.033). We could not validate these findings in multivariate analysis or in the TCGA dataset.ConclusionsLoss of 9p21.3 is not associated with outcome in a molecularly defined cohort of grade II glioma and therefore it remains unclear if loss of 9p21.3 can be used as additional marker of anaplasia or to guide treatment decisions. Trisomy of chromosome 7 in IDH mutated astrocytoma and PTEN mutations in IDH mutated oligodendroglioma are potential markers of poor prognosis, but require confirmation in larger series.
Highlights
In 2016 the World Health Organization Classification of Tumors of the Central Nervous System (WHO) was updated, resulting in a major change in the classification of diffuse gliomas [1]
In the present study we aimed to identify molecular prognostic markers for grade II IDH mutated astrocytoma and in grade II IDH mutated 1p19q-codeleted oligodendroglioma
As we were interested in additional markers for IDH mutated grade II glioma, 23 patient samples that were classified as IDH wildtype were excluded from further analyses. 207 patients were included in final analyses with a median follow-up of 6.9 years
Summary
In 2016 the World Health Organization Classification of Tumors of the Central Nervous System (WHO) was updated, resulting in a major change in the classification of diffuse gliomas [1]. Prognostication might be further improved if additional molecular markers can be identified that correlate with prognosis These markers may facilitate treatment decisions, in particular for early radiotherapy and adjuvant chemotherapy versus a wait and watch policy after surgery. At current prognostication of low grade glioma remains suboptimal and might be improved with additional markers. These may guide treatment decisions, in particular on early adjuvant therapy versus wait and see after surgery. We found a significant shorter overall survival with univariable analysis in IDH mutated astrocytoma patients with trisomy of chromosome 7 (Log rank P = 0.044) and in IDH mutated 1p/19q-codeleted oligodendroglioma patients with a PTEN mutation (Log rank P = 0.033). Trisomy of chromosome 7 in IDH mutated astrocytoma and PTEN mutations in IDH mutated oligodendroglioma are potential markers of poor prognosis, but require confirmation in larger series
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