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通过阵列比较基因组杂交分析揭示的一例成人毛细胞型星形细胞瘤中的基因变化。

Genetic changes observed in a case of adult pilocytic astrocytoma revealed by array CGH analysis.

作者信息

Pećina-Šlaus Nives, Gotovac Kristina, Kafka Anja, Tomas Davor, Borovečki Fran

机构信息

Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Šalata 12, 10000 Zagreb, Croatia ; Department of Biology, School of Medicine, University of Zagreb, Šalata 3, 10000 Zagreb, Croatia.

Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb School of Medicine, and University Hospital Center Zagreb, Šalata 2, 10 000 Zagreb, Croatia.

出版信息

Mol Cytogenet. 2014 Dec 23;7(1):95. doi: 10.1186/s13039-014-0095-2. eCollection 2014.

Abstract

BACKGROUND

A palette of copy number changes in a case of adult pilocytic astrocytoma analyzed by Array Comparative Genomic Hybridization (aCGH) is presented. Pilocytic astrocytomas are specific gliomas that are benign and biologically distinct and the molecular mechanisms responsible for their development remain unexplained. The aCGH was performed using SurePrint G3 Human CGH microarrays 4 × 180 K (Agilent Technologies). To ascertain whether some of the aberrations were of constitutive nature, we also analyzed the blood sample from the same patient.

RESULTS

The result of aCGH analysis demonstrated differences in the tumor tissue when compared to normal control on the array and also to autologous DNA from patient's blood. The total number of aberrations found in our case was 41 including 37 deletions and 4 amplifications. Whole chromosomal gains and losses were not observed. Collectively, our results showed three deletions and one amplification at 1p, two deletions at 2q, two deletions at 4q, two deletion at 5q, two deletions at 7p and two deletions at 7q; there were also three deletions at 8q, one deletion at 9p, one deletion at 10p, three deletions and one amplification at 10q. Chromosome 11 showed two deletions at 11p, while there was one deletion at 12p and one at 12q. Four deletions at 14q; two deletions at 15q, one amplification at 17q and one deletion at 17q; one deletion at 18p, two deletions at 22q and finally one deletion at Xp and one deletion and one amplification at Xq. Among the signaling pathways, olfactory transduction, Fc gamma R-mediated phagocytosis and p53 signaling pathway showed significant enrichment ascertained by gene ontology (GO) analysis using the DAVID software.

CONCLUSIONS

Our aCGH analysis is bringing subtle genomic alterations thus broadening genetic spectrum of adult pilocytic astrocytoma in order to offer new molecular biomarkers that will help in diagnostics and therapeutic decision-making.

摘要

背景

本文展示了通过阵列比较基因组杂交(aCGH)分析的一例成人毛细胞型星形细胞瘤的一系列拷贝数变化。毛细胞型星形细胞瘤是一种特殊的胶质瘤,具有良性且生物学特性独特的特点,其发生发展的分子机制仍不清楚。aCGH检测使用的是SurePrint G3人类CGH微阵列4×180K(安捷伦科技公司)。为确定某些畸变是否具有组成性,我们还分析了同一患者的血液样本。

结果

aCGH分析结果显示,与阵列上的正常对照以及患者血液中的自体DNA相比,肿瘤组织存在差异。我们病例中发现的畸变总数为41个,包括37个缺失和4个扩增。未观察到整条染色体的增减。总体而言,我们的结果显示1p有3个缺失和1个扩增,2q有2个缺失,4q有2个缺失,5q有2个缺失,7p有2个缺失,7q有2个缺失;8q也有3个缺失,9p有1个缺失,10p有1个缺失,10q有3个缺失和1个扩增。11号染色体在11p显示2个缺失,而12p有1个缺失,12q有1个缺失。14q有4个缺失;15q有2个缺失,17q有1个扩增和1个缺失;18p有1个缺失,22q有2个缺失,最后Xp有1个缺失,Xq有1个缺失和1个扩增。在信号通路中,嗅觉转导、FcγR介导的吞噬作用和p53信号通路经使用DAVID软件的基因本体(GO)分析显示有显著富集。

结论

我们的aCGH分析揭示了细微的基因组改变,从而拓宽了成人毛细胞型星形细胞瘤的遗传谱,以提供有助于诊断和治疗决策的新分子生物标志物。

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