Gene amplification: Mechanisms and involvement in cancer

Atsuka Matsui, Tatsuya Ihara, Hiraku Suda, Hirofumi Mikami, Kentaro Senba

    Research output: Contribution to journalArticle

    30 Citations (Scopus)

    Abstract

    Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate- resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

    Original languageEnglish
    Pages (from-to)567-582
    Number of pages16
    JournalBiomolecular Concepts
    Volume4
    Issue number6
    DOIs
    Publication statusPublished - 2013 Dec 1

    Fingerprint

    Gene Amplification
    Genes
    Neoplasm Genes
    Oncogenes
    Neoplasms
    Carcinogenesis
    Physiological Phenomena
    Tetrahydrofolate Dehydrogenase
    Amplification
    Drosophila melanogaster
    Methotrexate
    Genetic Recombination
    Machinery
    Fusion reactions
    Cells
    Pharmaceutical Preparations
    Therapeutics

    Keywords

    • Amplicon
    • Cancer
    • Development
    • Drug resistance
    • Microarray

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Cellular and Molecular Neuroscience

    Cite this

    Gene amplification : Mechanisms and involvement in cancer. / Matsui, Atsuka; Ihara, Tatsuya; Suda, Hiraku; Mikami, Hirofumi; Senba, Kentaro.

    In: Biomolecular Concepts, Vol. 4, No. 6, 01.12.2013, p. 567-582.

    Research output: Contribution to journalArticle

    Matsui, Atsuka ; Ihara, Tatsuya ; Suda, Hiraku ; Mikami, Hirofumi ; Senba, Kentaro. / Gene amplification : Mechanisms and involvement in cancer. In: Biomolecular Concepts. 2013 ; Vol. 4, No. 6. pp. 567-582.
    @article{710a381438324e679584cbc983098824,
    title = "Gene amplification: Mechanisms and involvement in cancer",
    abstract = "Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate- resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.",
    keywords = "Amplicon, Cancer, Development, Drug resistance, Microarray",
    author = "Atsuka Matsui and Tatsuya Ihara and Hiraku Suda and Hirofumi Mikami and Kentaro Senba",
    year = "2013",
    month = "12",
    day = "1",
    doi = "10.1515/bmc-2013-0026",
    language = "English",
    volume = "4",
    pages = "567--582",
    journal = "Biomolecular Concepts",
    issn = "1868-5021",
    publisher = "Walter de Gruyter GmbH & Co. KG",
    number = "6",

    }

    TY - JOUR

    T1 - Gene amplification

    T2 - Mechanisms and involvement in cancer

    AU - Matsui, Atsuka

    AU - Ihara, Tatsuya

    AU - Suda, Hiraku

    AU - Mikami, Hirofumi

    AU - Senba, Kentaro

    PY - 2013/12/1

    Y1 - 2013/12/1

    N2 - Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate- resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

    AB - Gene amplification was recognized as a physiological process during the development of Drosophila melanogaster. Intriguingly, mammalian cells use this mechanism to overexpress particular genes for survival under stress, such as during exposure to cytotoxic drugs. One well-known example is the amplification of the dihydrofolate reductase gene observed in methotrexate- resistant cells. Four models have been proposed for the generation of amplifications: extrareplication and recombination, the breakage-fusion-bridge cycle, double rolling-circle replication, and replication fork stalling and template switching. Gene amplification is a typical genetic alteration in cancer, and historically many oncogenes have been identified in the amplified regions. In this regard, novel cancer-associated genes may remain to be identified in the amplified regions. Recent comprehensive approaches have further revealed that co-amplified genes also contribute to tumorigenesis in concert with known oncogenes in the same amplicons. Considering that cancer develops through the alteration of multiple genes, gene amplification is an effective acceleration machinery to promote tumorigenesis. Identification of cancer-associated genes could provide novel and effective therapeutic targets.

    KW - Amplicon

    KW - Cancer

    KW - Development

    KW - Drug resistance

    KW - Microarray

    UR - http://www.scopus.com/inward/record.url?scp=84889801154&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84889801154&partnerID=8YFLogxK

    U2 - 10.1515/bmc-2013-0026

    DO - 10.1515/bmc-2013-0026

    M3 - Article

    C2 - 25436757

    AN - SCOPUS:84889801154

    VL - 4

    SP - 567

    EP - 582

    JO - Biomolecular Concepts

    JF - Biomolecular Concepts

    SN - 1868-5021

    IS - 6

    ER -