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原发性神经胶质瘤和配对复发肿瘤在 IDH1、TP53 和 TERTp 突变以及 MGMT、ATRX 缺失方面具有相似的生物学特征。

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

机构信息

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital; and School of Basic Medicine, The Fourth Military Medical University, Xi'an, Shaan Xi Province, China.

出版信息

Sci Rep. 2017 Oct 12;7(1):13038. doi: 10.1038/s41598-017-13272-9.

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.

摘要

星形细胞瘤是最常见的原发性恶性脑肿瘤。大多数星形细胞瘤在手术后的某个时候会复发。目前,放射治疗和化学疗法的联合应用并不能预防星形细胞瘤的复发。在这项研究中,我们研究了在星形细胞瘤复发过程中异柠檬酸脱氢酶 1(IDH1)、肿瘤蛋白 p53(TP53)和端粒酶逆转录酶启动子(TERTp)突变的一致性。我们还评估了疾病复发期间 O-6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)和 X 连锁的α-地中海贫血/智力低下(ATRX)的蛋白丢失。然后,我们使用 Kaplan-Meier 分析和 Cox 回归模型来确定这些发现对无进展生存期(PFS)的预后意义。我们的结果表明,在大多数情况下,IDH1、TP53 和 TERTp 突变状态以及 MGMT 和 ATRX 蛋白表达水平在复发期间是稳定的,这可能表明这些改变发生在星形细胞瘤的早期发展中。此外,在 IDH1 野生型组中,MGMT 阴性且 Ki67 指数较低的患者 PFS 较长。因此,我们建议 IDH1 突变联合 MGMT 表达水平和 Ki67 指数可能是评估星形细胞瘤患者 PFS 的有效生物标志物组合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4579/5638900/f43fcb3e2fcc/41598_2017_13272_Fig1_HTML.jpg

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