Abstract
The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACT-NOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations at reasonable cost. The purpose of this study was to identify a precise, cost-effective method for stratifying the prognosis of IDH-wild-type astrocytoma. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analysed for 40 patients who underwent first surgery. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 using cIMPACT-NOW update 3 criteria and all had either TERTp mutation or EGFR amplification. Kaplan–Meier analysis confirmed the prognostic significance of cIMPACT-NOW criteria, and World Health Organization grade was also prognostic. Cox regression hazard model identified independent significant prognostic indicators of PTEN loss (risk ratio, 9.75; p < 0.001) and PDGFRA amplification (risk ratio, 13.9; p = 0.002). The classification recommended by cIMPACT-NOW update 3 could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytoma.
Highlights
The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear
Oligodendroglioma was defined as a glioma with both IDH-mutation and 1p/19q codeletion, and the K27M mutation in H3F3A or less common HIST1H3B was included in the criteria for diffuse midline glioma, H3K27M-mutant[5]
All samples received integrated diagnosis based on the World Health Organization (WHO) 2016 classification, and 42 tumours from 42 patients (31 men, 11 women) were classified as IDH-wild-type astrocytoma
Summary
The characteristics of IDH-wild-type lower-grade astrocytoma remain unclear. According to cIMPACTNOW update 3, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+ 7/− 10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. HIST1H3B Histone cluster 1 H3 family member b IDH Isocitrate dehydrogenase MDM2 Murine double minute 2 MGMTp O6-Methylguanine-DNA methyltransferase promoter MLPA Multiplex ligation-dependent probe amplification NFKBIA Nuclear factor kappa-B inhibitor alpha OS Overall survival PDGFRA Platelet-derived growth factor receptor A PTEN Phosphatase and tensin homolog deleted from chromosome 10 qMSP Quantitative methylation-specific PCR TCGA The Cancer Genome Atlas TERT Telomerase reverse transcriptase TERTp Telomerase reverse transcriptase promoter TP53 Tumour protein p53 WHO World Health Organization. Glioblastoma, grade IV (GBM) is the most aggressive and major subtype of glioma, while diffuse astrocytoma, grade II (DA) and anaplastic astrocytoma, grade III (AA) are lower-grade astrocytomas All these pathological entities had been classified mainly based on histology in the 2007 World Health Organization (WHO) classification of central nervous system tumours[2]. Oligodendroglioma was defined as a glioma with both IDH-mutation and 1p/19q codeletion, and the K27M mutation in H3F3A or less common HIST1H3B was included in the criteria for diffuse midline glioma, H3K27M-mutant[5]
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