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Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study.

高级别胶质瘤生物标志物的发生率及其对东南亚队列生存的影响-一项基于人群的研究。

  • 影响因子:3.29
  • DOI:10.1186/s12885-020-6536-x
  • 作者列表:"Ang SYL","Lee L","See AAQ","Ang TY","Ang BT","King NKK
  • 发表时间:2020-01-31
Abstract

BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

摘要

背景: 胶质瘤由一组异质性肿瘤组成。本研究旨在报道 O6-methylguanine-DNA-methyltransferase (MGMT) 启动子甲基化、 1p19q 共缺失、异柠檬酸脱氢酶 (IDH) 基因突变的发生率。和在种族多样化人群中高级别胶质瘤中 α-地中海贫血/精神发育迟滞综合征 X 连锁 (ATRX) 的失活突变。 方法: 获得 2013年1月至 2017年3月在我们机构接受高级别胶质瘤手术的患者记录。记录患者的年龄、性别、种族、 Karnofsky 性能量表 (KPS) 评分、日常生活活动能力 (ADLs) 、肿瘤部位和生物标志物状态。使用卡方和 Mann-Whitney U 检验、 Kaplan-Meier 估计和 log-rank 检验分析数据。 结果: 入选患者 181 例 (ⅲ 级胶质瘤 56 例,ⅳ 级胶质瘤 125 例)。在 ⅲ 级组中,55% 有 MGMT 启动子甲基化,41% 有 1p19q 共缺失,35% 有 IDH1 突变,无 ATRX 缺失。在 IV 级组中,30% 有 MGMT 启动子甲基化,2% 有 1p19q 共缺失,15% 有 IDH1 突变,8% 有 ATRX 缺失。在调整了年龄、手术和术前 ADL 状态的影响后,发现只有 MGMT 启动子甲基化与 ⅲ 级患者更长的总生存期显著相关 (p = 0.024) 和 IV 患者 (p = 0.006)。 结论: 发现 MGMT 启动子甲基化和 IDH1 突变的发生率与全球报道的发生率相当,但在我们的队列中 1p19q 共缺失和 ATRX 缺失的发生率似乎较低。在我们的队列中,MGMT 启动子甲基化与总生存期增加相关,可能作为有利的预后因素。

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影响因子:4.01
发表时间:2020-01-30
DOI:10.1002/mrm.28183
作者列表:["Tiwari V","Mashimo T","An Z","Vemireddy V","Piccirillo S","Askari P","Hulsey KM","Zhang S","de Graaf RA","Patel TR","Pan E","Mickey BE","Maher EA","Bachoo RM","Choi C"]

METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.

影响因子:3.29
发表时间:2020-01-31
来源期刊:BMC cancer
DOI:10.1186/s12885-020-6536-x
作者列表:["Ang SYL","Lee L","See AAQ","Ang TY","Ang BT","King NKK"]

METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.

翻译标题与摘要 下载文献
影响因子:5.34
发表时间:2020-01-31
DOI:10.1186/s13046-020-1534-z
作者列表:["Abbruzzese C","Matteoni S","Persico M","Villani V","Paggi MG"]

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