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生物标志物分类与恶性脑胶质瘤的治疗决策

Biomarkers classification and therapeutic decision-making for malignant gliomas.

机构信息

Department of Pathology and Genomic Medicine, The Methodist Hospital, 6565 Fannin St, M227, Houston, TX 77030, USA.

出版信息

Curr Treat Options Oncol. 2012 Dec;13(4):417-36. doi: 10.1007/s11864-012-0210-8.

DOI:10.1007/s11864-012-0210-8
PMID:22956341
Abstract

Diffuse gliomas are the most common primary brain tumors, with glioblastoma (GBM) encompassing more than 50 % of all cases. Despite aggressive therapy, patients nearly always succumb to their disease and the survival for patients with GBM is approximately 1 year. During past years, numerous scientific contributions have reshaped the field of neuro-oncology and neuropathology. A series of molecular discoveries have shed light on new pathogenic mechanisms, as well as new prognostic and predictive biomarkers with clinical relevance. The current World Health Organization (WHO) classification system is solely based on morphologic criteria; however, there is accumulated evidence that tumors with similar histology have distinct molecular signatures with a clinically significant impact on treatment response and survival. Molecular markers and signatures could be incorporated into the glioma classification and grading system to mirror the clinical outcomes. Additionally, molecular markers could lead to a redefinition of currently controversial entities, such as mixed oligoastrocytomas. Newly discovered molecular alterations also have the potential to become targets for future drug development. Despite tremendous progress in the past decade, therapeutic progress for diffuse gliomas has been slow. A further understanding of glioma biology, in concert with well-designed clinical trials, is necessary to identify more putative molecular biomarkers and unravel the mysteries in the pathogenic mechanisms that trigger this menacing disease.

摘要

弥漫性神经胶质瘤是最常见的原发性脑肿瘤,其中胶质母细胞瘤(GBM)占所有病例的 50%以上。尽管采用了积极的治疗方法,但几乎所有患者最终都会死于该疾病,GBM 患者的生存时间约为 1 年。在过去的几年中,大量的科学贡献改变了神经肿瘤学和神经病理学领域。一系列的分子发现揭示了新的发病机制,以及具有临床相关性的新的预后和预测生物标志物。目前的世界卫生组织(WHO)分类系统仅基于形态学标准;然而,有越来越多的证据表明,具有相似组织学的肿瘤具有不同的分子特征,对治疗反应和生存有明显的临床影响。分子标志物和特征可以纳入神经胶质瘤的分类和分级系统,以反映临床结果。此外,分子标志物可以重新定义目前存在争议的实体,如混合性少突胶质细胞瘤。新发现的分子改变也有可能成为未来药物开发的靶点。尽管在过去十年中取得了巨大进展,但弥漫性神经胶质瘤的治疗进展缓慢。为了确定更多可能的分子生物标志物并揭示导致这种威胁生命的疾病的发病机制中的奥秘,有必要进一步了解神经胶质瘤的生物学,并结合精心设计的临床试验。

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Life (Basel). 2022 Oct 21;12(10):1673. doi: 10.3390/life12101673.
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High expression of VEGF and PI3K in glioma stem cells provides new criteria for the grading of gliomas.胶质瘤干细胞中VEGF和PI3K的高表达为胶质瘤分级提供了新的标准。
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High metallothionein predicts poor survival in glioblastoma multiforme.高金属硫蛋白预示多形性胶质母细胞瘤患者预后不良。

本文引用的文献

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The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.2016 年世界卫生组织中枢神经系统肿瘤分类:概述。
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KIAA1549-BRAF fusions and IDH mutations can coexist in diffuse gliomas of adults.成人弥漫性神经胶质瘤中可同时存在 KIAA1549-BRAF 融合和 IDH 突变。
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Glial progenitors as targets for transformation in glioma.神经胶质前体细胞作为胶质瘤转化的靶点。
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Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing.由于恶性星形细胞瘤的病理肿瘤样本较小而导致的诊断差异可通过异柠檬酸脱氢酶1(IDH1)检测来克服。
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Prognostic and predictive biomarkers in adult and pediatric gliomas: toward personalized treatment.成人和儿童胶质瘤中的预后和预测生物标志物:走向个性化治疗
Front Oncol. 2014 Mar 24;4:47. doi: 10.3389/fonc.2014.00047. eCollection 2014.
9
Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods.恶性胶质瘤:使用先进定量成像方法进行诊断、治疗及早期反应评估的当前观点
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10
Clinicopathologic characteristics of brain tumors are associated with the presence and patterns of TP53 mutations: evidence from the IARC TP53 Database.脑肿瘤的临床病理特征与 TP53 突变的存在和模式相关:来自 IARC TP53 数据库的证据。
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少突胶质细胞瘤、少突星形细胞瘤和星形细胞瘤中的 CIC 和 FUBP1 突变。
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Frequent BRAF gain in low-grade diffuse gliomas with 1p/19q loss.低级别弥漫性神经胶质瘤伴 1p/19q 缺失时频繁出现 BRAF 获得。
Brain Pathol. 2012 Nov;22(6):834-40. doi: 10.1111/j.1750-3639.2012.00601.x. Epub 2012 Jun 1.
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The role of BRAF V600 mutation in melanoma.BRAF V600 突变在黑色素瘤中的作用。
J Transl Med. 2012 Jul 9;10:85. doi: 10.1186/1479-5876-10-85.
6
No prognostic value of IDH1 mutations in a series of 100 WHO grade II astrocytomas.IDH1 突变在 100 例 WHO 分级 II 星形细胞瘤中的预后价值不明确。
J Neurooncol. 2012 Aug;109(1):15-22. doi: 10.1007/s11060-012-0863-y. Epub 2012 Apr 19.
7
Detection of "oncometabolite" 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma.磁共振分析检测“致癌代谢物”2-羟戊二酸作为胶质瘤 IDH1/2 突变的生物标志物。
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8
IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas.异柠檬酸脱氢酶突变作为低级别星形细胞瘤(WHO 分级 II)及其连续的继发性高级别神经胶质瘤的早期且一致的标志物。
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Molecular pathogenesis of IDH mutations in gliomas.胶质瘤中 IDH 突变的分子发病机制。
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10
1P19Q loss but not IDH1 mutations influences WHO grade II gliomas spontaneous growth.1p19q 缺失而非 IDH1 突变影响 WHO 分级 II 级胶质瘤的自发性生长。
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