Genomic Markers for Glioblastoma Multiforme, Revealed by Array CGH Analysis
Dimova Ivanka, Hadjiolova Radka, Naydenov Emanuil, Nesheva Desislava, Toncheva Draga
Current Journal of Applied Science and Technology · pp. 1540–1553 · Published 11 Feb 2014
10.9734/BJAST/2014/8487Abstract
Aims: Despite of intensive studies of glioblastoma multiforme, still no unified concept for the most important specific molecular alterations exists for this tumor type. The method of array CGH has great potential for molecular characterization of glioblastoma. The aim of our study was to determine the type, frequency and fine mapping of unbalanced genomic changes and to suggest candidate genes for the emergence and development of brain tumors. Study Design: Ten tumor samples were collected from patients with glioblastoma multiforme after taking informed consent. Histological examination was done to confirm the presence of tumor cells in more than 75% of the samples. DNA was isolated from each tumor sample. Place and Duration of Study: The material was collected in Department of Neurosurgery (Medical University Sofia) and processed for analysis in Department of Medical genetics (Medical University Sofia) between June 2010 and December 2011. Methodology: We used the method of array CGH with BAC clones, covering the entire genome, for investigation of copy number changes in tumors. We applied specific software microarray analysis (Blue Fuse, Blue Gnome, Cambridge, UK). For fine mapping of the most significant aberrations and to identify possible candidate genes: 1) we identified BAC clones with aberrations of high amplitude (ratio T / H> 0.5 for gains and <-0.5 for losses); 2) we select only those clones that have a frequency of aberrations more than 30% and have at least one adjacent clone with the same aberration. Doing this we also determined the smallest regions of overlap (SRO) of aberrations that occur in at least 50% of tumors. Results: Trisomy 7 (70%) and monosomy 10 (80%) were the most common big aberrations in tumors. Regional aberrations across all chromosomes were characterized in details. The most frequent were: amplification of 1q43-1q44 (50-70%), deletion 1p36 (60%), gains 9p11-9p13 (50%), deletion 18q22 (50%), gains of 20q11-q13 (50%), loss of 22q12 (50%), deletion Xp21 (50%). By determination of smallest regions of overlap and based on their function, we suggested potential candidate-oncogenes (RGS7, CDK5, OPN3, CDK5RAP1, PTPN1) and tumor-suppressor genes (NF2 and OSM). Conclusion: Our study provide with basis for further studies in which the role of identified candidate-genes will be validated by other molecular genetics methods and at other levels - transcriptional and protein. This will lead to significant advances in knowledge of glioblastoma multiforme and suggestion of new more effective molecular-based prognostic and therapeutic indicators.
References (26)
- 1 An Integrated Genomic Analysis of Human Glioblastoma Multiforme [DOI]
- 2 High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays [DOI]
- 3 Matrix-based comparative genomic hybridization: Biochips to screen for genomic imbalances [DOI]
- 4 Oncostatin M: a growth regulator produced by differentiated histiocytic lymphoma cells. [DOI]
- 5 Integrated Array-Comparative Genomic Hybridization and Expression Array Profiles Identify Clinically Relevant Molecular Subtypes of Glioblastoma [DOI]
- 6 Gene Expression Profile of Glioblastoma Multiforme Invasive Phenotype Points to New Therapeutic Targets [DOI]
- 7 Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis [DOI]
- 8 Homologs of vertebrate Opn3 potentially serve as a light sensor in nonphotoreceptive tissue [DOI]
- 9 A survey of glioblastoma genomic amplifications and deletions [DOI]
- 10 Detection of Multiple Gene Amplifications in Glioblastoma Multiforme Using Array-Based Comparative Genomic Hybridization [DOI]
- 11 Identification of novel candidate target genes in amplicons of Glioblastoma multiforme tumors detected by expression and CGH microarray profiling [DOI]
- 12 Intratumoral Patterns of Genomic Imbalance in Glioblastomas [DOI]
- 13 Identification of a Neuronal Cdk5 Activator-binding Protein as Cdk5 Inhibitor [DOI]
- 14 The prognostic relevance of molecular alterations in glioblastomas for patients age < 50 years [DOI]
- 15 Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells [DOI]
- 16 Mutational analysis of patients with neurofibromatosis 2.
- 17 Genetic analysis of glioblastoma multiforme provides evidence for subgroups within the grade [DOI]
- 18 Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array [DOI]
- 19 Exploratory Analysis of the Copy Number Alterations in Glioblastoma Multiforme [DOI]
- 20 Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas [DOI]
- 21 Gains at the 1p36 Chromosomal Region Are Associated With Symptomatic Leptomeningeal Dissemination of Supratentorial Glioblastomas [DOI]
- 22 Novel amplicons on the short arm of chromosome 7 identified using high resolution array CGH contain over expressed genes in addition to EGFR in glioblastoma multiforme [DOI]
- 23 Chromosome arm 1q gain associated with good response to chemotherapy in a malignant glioma [DOI]
- 24 Integration of Global Spectral Karyotyping, CGH Arrays, and Expression Arrays Reveals Important Genes in the Pathogenesis of Glioblastoma Multiforme [DOI]
- 25 Array CGH in Brain Tumors [DOI]
- 26 MOLECULAR.CELL.BIOLOGY 5TH.ED
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