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Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.应用单核苷酸多态性微阵列技术对胶质母细胞瘤 7、9 和 10 号染色体改变的详细特征分析。
J Mol Diagn. 2011 Nov;13(6):634-47. doi: 10.1016/j.jmoldx.2011.06.003. Epub 2011 Aug 30.
2
Molecular genetic alterations in glioblastomas with oligodendroglial component.具有少突胶质细胞成分的胶质母细胞瘤中的分子遗传学改变。
Acta Neuropathol. 2001 Apr;101(4):311-20. doi: 10.1007/s004010000258.
3
New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile.胶质母细胞瘤中 EGFR 扩增的新模式及其与基因表达谱的基因拷贝数的关系。
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4
Monosomy of chromosome 10 associated with dysregulation of epidermal growth factor signaling in glioblastomas.10号染色体单体与胶质母细胞瘤中表皮生长因子信号传导失调相关。
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Cytogenetic and molecular genetic study on granular cell glioblastoma: a case report.颗粒细胞神经胶质瘤的细胞遗传学和分子遗传学研究:病例报告。
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8
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Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors.通向多形性胶质母细胞瘤的途径:65例星形细胞瘤基因改变的分子分析
J Neurosurg. 1994 Sep;81(3):427-36. doi: 10.3171/jns.1994.81.3.0427.

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Proteomics separates adult-type diffuse high-grade gliomas in metabolic subgroups independent of 1p/19q codeletion and across IDH mutational status.蛋白质组学可将代谢亚群中的成人型弥漫性高级别神经胶质瘤与 1p/19q 缺失代码和 IDH 突变状态分开。
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本文引用的文献

1
Age-dependent prognostic effects of EGFR/p53 alterations in glioblastoma: study on a prospective cohort of 140 uniformly treated adult patients.年龄依赖性 EGFR/p53 改变对胶质母细胞瘤预后的影响:一项前瞻性队列研究,纳入了 140 例经统一治疗的成年患者。
J Clin Pathol. 2010 Aug;63(8):687-91. doi: 10.1136/jcp.2009.074898.
2
Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease.对儿科高级别神经胶质瘤进行综合分子遗传学分析揭示了与成人疾病的关键差异。
J Clin Oncol. 2010 Jun 20;28(18):3061-8. doi: 10.1200/JCO.2009.26.7252. Epub 2010 May 17.
3
A hierarchy of self-renewing tumor-initiating cell types in glioblastoma.胶质母细胞瘤中自我更新肿瘤起始细胞类型的层次结构。
Cancer Cell. 2010 Apr 13;17(4):362-75. doi: 10.1016/j.ccr.2009.12.049.
4
New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile.胶质母细胞瘤中 EGFR 扩增的新模式及其与基因表达谱的基因拷贝数的关系。
Mod Pathol. 2010 Jun;23(6):856-65. doi: 10.1038/modpathol.2010.62. Epub 2010 Mar 19.
5
Integrated genomic profiling identifies candidate genes implicated in glioma-genesis and a novel LEO1-SLC12A1 fusion gene.综合基因组分析鉴定出与胶质瘤发生相关的候选基因,并发现一个新的 LEO1-SLC12A1 融合基因。
Genes Chromosomes Cancer. 2010 Jun;49(6):509-17. doi: 10.1002/gcc.20760.
6
The landscape of somatic copy-number alteration across human cancers.人类癌症中体细胞拷贝数改变的全景。
Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.
7
Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas.利用单核苷酸多态性芯片进行全基因组分析鉴定小儿脑胶质瘤中的新型染色体不平衡。
Neuro Oncol. 2010 Feb;12(2):153-63. doi: 10.1093/neuonc/nop001. Epub 2009 Oct 15.
8
Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets.对小儿弥漫性内在脑桥胶质瘤的全基因组分析突出了血小板衍生生长因子受体α和多聚(ADP-核糖)聚合酶作为潜在的治疗靶点。
J Clin Oncol. 2010 Mar 10;28(8):1337-44. doi: 10.1200/JCO.2009.25.5463. Epub 2010 Feb 8.
9
Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1.整合基因组分析确定了具有 PDGFRA、IDH1、EGFR 和 NF1 异常的胶质母细胞瘤的临床相关亚型。
Cancer Cell. 2010 Jan 19;17(1):98-110. doi: 10.1016/j.ccr.2009.12.020.
10
Interpreting aCGH-defined karyotypic changes in gliomas using copy number status, loss of heterozygosity and allelic ratios.运用拷贝数状态、杂合性缺失和等位基因比解读神经胶质瘤中 aCGH 定义的核型改变。
Exp Mol Pathol. 2010 Feb;88(1):82-9. doi: 10.1016/j.yexmp.2009.09.014. Epub 2009 Oct 7.

应用单核苷酸多态性微阵列技术对胶质母细胞瘤 7、9 和 10 号染色体改变的详细特征分析。

Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays.

机构信息

Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

出版信息

J Mol Diagn. 2011 Nov;13(6):634-47. doi: 10.1016/j.jmoldx.2011.06.003. Epub 2011 Aug 30.

DOI:10.1016/j.jmoldx.2011.06.003
PMID:21884817
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3194060/
Abstract

Glioblastomas are cytogenetically heterogeneous tumors that frequently display alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single-nucleotide polymorphism arrays to investigate genome-wide copy number alterations and loss of heterozygosity in 35 primary glioblastomas. We focused on the identification and detailed characterization of alterations involving the most frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns of alteration for these chromosomes, and validation of their prognostic impact in a larger series of tumors from public databases. Gains of chromosome 7 (97%), with or without epidermal growth factor receptor (EGFR) amplification, and losses of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such alterations defined five different cytogenetic groups with a significant effect on patient survival; notably, EGFR amplification (29%) was associated with a better survival among older patients, as confirmed by multivariate analysis of a larger series of glioblastomas from the literature. In addition, our results provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B, MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the cytogenetic heterogeneity of glioblastomas and suggest that their stratification based on combined assessment of cytogenetic alterations involving chromosomes 7, 9, and 10 may contribute to the prognostic evaluation of glioblastomas.

摘要

胶质母细胞瘤是细胞遗传学上异质性的肿瘤,经常显示染色体 7、9p 和 10q 的改变。我们使用高密度(500K)单核苷酸多态性微阵列来研究 35 例原发性胶质母细胞瘤的全基因组拷贝数改变和杂合性丢失。我们专注于鉴定和详细描述涉及最常改变的染色体(染色体 7、9 和 10)的改变,基于这些染色体改变的细胞遗传学模式鉴定胶质母细胞瘤的不同预后亚组,并在来自公共数据库的更大系列肿瘤中验证其预后影响。染色体 7 的增益(97%),无论是否有表皮生长因子受体(EGFR)扩增,以及染色体 9p(83%)和 10(91%)的丢失是最常见的改变。这些改变定义了五个不同的细胞遗传学组,对患者的生存有显著影响;值得注意的是,EGFR 扩增(29%)与老年患者的生存改善相关,这在对来自文献的更大系列胶质母细胞瘤的多变量分析中得到了证实。此外,我们的结果提供了进一步的证据,证明了其他基因(如 EGFR、CDKN2A/B、MTAP)在胶质母细胞瘤发病机制中的相关性。总之,我们的结果证实了胶质母细胞瘤的细胞遗传学异质性,并表明基于涉及染色体 7、9 和 10 的细胞遗传学改变的综合评估对胶质母细胞瘤的预后评估可能有帮助。