ATRX突变与胶质母细胞瘤：DNA损伤修复受损、端粒替代延长及基因不稳定。
ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability.
作者信息
Koschmann Carl, Lowenstein Pedro R, Castro Maria G
机构信息
Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Department of Neurosurgery and Department of Cell and Developmental Biology, University of Michigan School of Medicine , Ann Arbor, MI, USA.
出版信息
Mol Cell Oncol. 2016 Apr 27;3(3):e1167158. doi: 10.1080/23723556.2016.1167158. eCollection 2016 May.
Abstract
Alpha thalassemia/mental retardation syndrome X-linked (ATRX) is mutated in nearly a third of pediatric glioblastoma (GBM) patients. We developed an animal model of ATRX-deficient GBM. Using this model combined with analysis of multiple human glioma genome-wide datasets, we determined that ATRX mutation leads to genetic instability, impaired non-homologous end joining, and alternate lengthening of telomeres (ALT).
摘要
X连锁的α地中海贫血/智力迟钝综合征（ATRX）在近三分之一的儿童胶质母细胞瘤（GBM）患者中发生突变。我们建立了ATRX缺陷型GBM的动物模型。利用该模型并结合对多个人类胶质瘤全基因组数据集的分析，我们确定ATRX突变会导致基因不稳定、非同源末端连接受损以及端粒的替代延长（ALT）。
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本文引用的文献
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ATRX loss promotes tumor growth and impairs nonhomologous end joining DNA repair in glioma.ATRX缺失促进胶质瘤的肿瘤生长并损害非同源末端连接DNA修复。
Sci Transl Med. 2016 Mar 2;8(328):328ra28. doi: 10.1126/scitranslmed.aac8228.
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Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors.端粒替代延长使癌细胞对 ATR 抑制剂高度敏感。
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Is non-homologous end-joining really an inherently error-prone process?非同源末端连接真的是一个固有易错的过程吗？
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Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress.X 连锁的α地中海贫血/智力迟钝综合征基因产物 ATRX 对于适当的复制启动和细胞对复制应激的抗性是必需的。
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Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.组蛋白 H3.3 和染色质重塑基因中的驱动突变与儿童弥漫性脑桥胶质瘤。
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Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity.胶质母细胞瘤中O6-甲基鸟嘌呤甲基转移酶（MGMT）启动子甲基化与临床结局的相关性及调节MGMT活性的临床策略。
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Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.放疗联合同步及辅助替莫唑胺治疗胶质母细胞瘤
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The ATRX syndrome protein forms a chromatin-remodeling complex with Daxx and localizes in promyelocytic leukemia nuclear bodies.ATRX综合征蛋白与Daxx形成一种染色质重塑复合物，并定位于早幼粒细胞白血病核小体中。
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