Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss
Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss
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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 丢失方面具有相似的生物学特征
DOI：
10.1038/s41598-017-13272-9
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发表时间：
2017-10-12
影响因子：
4.6
通讯作者：
Wang，Zhe
中科院分区：
文献类型：
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作者：
Li，Xia;Wei，Jie;Wang，Zhe
星形细胞肿瘤是最常见的原发恶性脑肿瘤。大多数星形细胞肿瘤会在手术后的某个时间复发。目前，放化疗的结合并不能预防星形细胞肿瘤的复发。在本研究中，我们研究了异柠檬酸脱氢酶1(IDH1)、肿瘤蛋白P53(TP53)和端粒酶逆转录酶启动子(TERTp)突变与星形细胞肿瘤复发的一致性。我们还评估了O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)和α-地中海贫血/智力低下X连锁(ATRX)在疾病复发过程中的蛋白丢失情况。然后，我们使用Kaplan-Meier分析和Cox回归模型来确定这些发现在无进展生存(PFS)方面的预后意义。我们的结果显示，在大多数病例中，IDH1、TP53和TERT突变状态以及MGMT和ATRX蛋白的表达水平在复发期间是稳定的，这可能表明这些变化发生在星形细胞肿瘤发生的早期。此外，在IDH1野生型组中，MGMT阴性且Ki67指数低的患者的PFS较长。因此，我们认为IDH1突变结合MGMT表达水平和Ki67指数可能是评估星形细胞肿瘤患者预后的一个有效的生物标志物组合。
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,TP53andTERTpmutation 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, inIDH1wild type group, the patients who were negative for MGMT and had a low Ki67 index showed a longer PFS. Therefore, we suggest thatIDH1mutation combined with MGMT expression level and Ki67 index might be an effective biomarker panel for evaluating the PFS of patients with astrocytic tumours.