Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss

原发性星形细胞肿瘤和配对复发在 IDH1、TP53 和 TERTp 突变以及 MGMT、ATRX 缺失方面具有相似的生物学特征

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作者:Xia Li, Jie Wei, Yixiong Liu, Peifeng Li, Linni Fan, Yingmei Wang, Mingyang Li, Danhui Zhao, Zhou Yu, Jing Ye, Ying Guo, Qingguo Yan, Shuangping Guo, Zhe Wang

Abstract

Astrocytic tumours are the most common type of primary malignant brain tumour. Most astrocytic tumours will recur at some point after surgery. Currently, the combination of radiotherapy and chemotherapy does not prevent the recurrence of astrocytic tumours. In this study, we investigated the consistency in isocitrate dehydrogenase 1 (IDH1), tumour protein p53 (TP53) and telomerase reverse transcriptase promoter (TERTp) mutations during astrocytic tumour recurrence. We also evaluated the protein loss of O-6-methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) during disease recurrence. We then determined the prognostic significance of these findings in terms of progression-free survival (PFS) using Kaplan-Meier analysis and Cox regression models. Our results showed that in most cases, IDH1, TP53 and TERTp mutation status and MGMT and ATRX protein expression levels were stable during recurrence, which may indicate that these alterations occurred early in astrocytic tumour development. Furthermore, in IDH1 wild type group, the patients who were negative for MGMT and had a low Ki67 index showed a longer PFS. Therefore, we suggest that IDH1 mutation combined with MGMT expression level and Ki67 index might be an effective biomarker panel for evaluating the PFS of patients with astrocytic tumours.

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