Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma.

Brain Tumor Research Center, Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA.
Clinical Cancer Research (Impact Factor: 7.84). 05/2005; 11(8):2907-18. DOI: 10.1158/1078-0432.CCR-04-0708
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glioma is a type of tumor that develops in the central nerve system, mainly the brain. Alterations of genomic sequence and sequence segments (such as copy number variations or CNV and copy neutral loss of heterozygosities or cnLOH) are thought to be a major determinant of the tumor grade. We mapped genomic variations between low-grade and high-grade gliomas (LGG and HGG) in Chinese population based on Illumina's Beadchip and validated the results using real-time qPCR. AT THE CYTOBAND LEVEL, WE DISCOVERED: (1) unique losses in LGG on 5q, 8p and 11q, and in HGG on 6q, 11p, 13q and 19q; (2) unique gains in the LGG on 1p and in HGG at 5p, 7p, 7q and 20q; and (3) cnLOH in HGG only on 3q, 8q, 10p, 14q, 15q, 17p, 17q, 18q and 21q. Subsequently, we confirmed well-characterized oncogenes among tumor-related loci (such as and ) and detected novel genes that gained chromosome sequences (such as , , and ) in both LGG and HGG. In addition, we found gains, losses, and cnLOH in several genes, including , , and , in multiple samples. Mapping grade-associated pathways and their related gene ontology (GO) terms, we classified LGG-associated functions as ", " and " and the HGG-associated as ", " and ". LGG and HGG appear to have different molecular signatures in genomic variations and our results provide invaluable information for the diagnosis and treatment of gliomas in patients with variable duration or diverse tumor differentiation.
    PLoS ONE 01/2013; 8(2):e57168. · 3.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Alternative lengthening of telomeres (ALT) is one of the two known telomere length maintenance mechanisms that are essential for the unlimited proliferation potential of cancer cells. Existing methods for detecting ALT in tumors require substantial amounts of tumor material and are labor intensive, making it difficult to study prevalence and prognostic significance of ALT in large tumor cohorts. Here, we present a novel strategy utilizing telomere quantitative PCR to diagnose ALT. The protocol is more rapid than conventional methods and scrutinizes two distinct characteristics of ALT cells concurrently: long telomeres and the presence of C-circles (partially double-stranded circles of telomeric C-strand DNA). Requiring only 30 ng of genomic DNA, this protocol will facilitate large-scale studies of ALT in tumors and can be readily adopted by clinical laboratories.
    Nucleic Acids Research 08/2012; · 8.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    01/2013: pages 357-388; , ISBN: 978-953-51-1058-3