Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma
ABSTRACT Alterations of DNA copy number are believed to be important indicators of tumor progression in human astrocytoma. We used an array of bacterial artificial chromosomes to map relative DNA copy number in 50 primary glioblastoma multiforme tumors at approximately 1.4-Mb resolution. We identified 33 candidate sites for amplification and homozygous deletion in these tumors. We identified three major genetic subgroups within these glioblastoma multiforme tumors: tumors with chromosome 7 gain and chromosome 10 loss, tumors with only chromosome 10 loss in the absence of chromosome 7 gain, and tumors without copy number change in chromosomes 7 or 10. The significance of these genetic groups to therapeutics needs further study.
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ABSTRACT: Cytogenetics is the branch of genetics that studies the cell activity focusing mainly on the chromosome structure, organization and function, isolated or as the whole karyotype, in order to understand aspects of cell biology, evolution or implicated diseases. The behavior of DNA and genes is greatly constrained by the fact that they are incorporated into chromosomes. The DNA is associated with proteins that control and catalyze the processes of transcription and replication. Gene expression is controlled by modifications in histones and by chromatin remodeling complexes. It can also be influenced by the position of the gene in the chromosome. Hence, errors in chromosome behavior are an important cause of ill-health. The presence of chromosomal abnormalities is usual in cancer, and specific chromosome abnormality may often be one of the first events in the development of cancer. The importance of cytogenetic analysis in oncology is demonstrated by the number of researches made on this area since the discovery of the Philadelphia chromosome, a 9/22 translocation, which is seen in chronic myelogenous leukemia (CML) patients. The focus of these studies is the relation between specific chromosome alterations to prognosis, drug resistance and diagnosis for some tumors entities. Moreover, DNA repair problems and others genomic stability pathways defects may lead to genome-wide genetic instability, which can drive further cancer progression. Although chromosome rearrangements are mainly used as markers in hematologic cancers, these alterations have been increasingly studied in solid tumors (90% of all human malignancies), showing that chromosomal numerical/structural aberrations are common in this kind of neoplasia.Clinical Management and Evolving Novel Therapeutic Strategies for Patients with Brain Tumors, 1 edited by Terry Lichtor, 01/2013: chapter 17: pages 357-388; InTech., ISBN: 978-953-51-1058-3
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ABSTRACT: The molecular pathogenesis of pediatric pilocytic astrocytoma (PA) is not well defined. Previous cytogenetic and molecular studies have not identified nonrandom genetic aberrations. To correlate differential gene expression and genomic copy number aberrations (CNAs) in PA, we have used Affymetrix GeneChip HG_U133A to generate gene expression profiles of 19 pediatric patients and the SpectralChip 2600 to investigate CNAs in 11 of these tumors. Hierarchical clustering according to expression profile similarity grouped tumors and controls separately. We identified 1844 genes that showed significant differential expression between tumor and normal controls, with a large number clearly influencing phosphatidylinositol and mitogen-activated protein kinase signaling in PA. Most CNAs identified in this study were single-clone alterations. However, a small region of loss involving up to seven adjacent clones at 7q11.23 was observed in seven tumors and correlated with the underexpression of BCL7B. Loss of four individual clones was also associated with reduced gene expression including SH3GL2 at 9p21.2-p23, BCL7A (which shares 90% sequence homology with BCL7B) at 12q24.33, DRD1IP at 10q26.3, and TUBG2 and CNTNAP1 at 17q21.31. Moreover, the down-regulation of FOXG1B at 14q12 correlated with loss within the gene promoter region in most tumors. This is the first study to correlate differential gene expression with CNAs in PA.Neoplasia (New York, N.Y.) 09/2008; 10(8):757-72. DOI:10.1593/neo.07914 · 5.40 Impact Factor
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ABSTRACT: Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses.Genes & Development 12/2007; 21(21):2683-710. DOI:10.1101/gad.1596707 · 12.64 Impact Factor