國家衛生研究院 NHRI:Item 3990099045/2230
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    题名: High-frequency Alu-mediated genomic recombination/deletion within the caspase-activated DNase gene in human hepatoma
    作者: Hsieh, SY;Chen, WY;Yeh, TS;Sheen, IS;Huang, SF
    贡献者: Division of Molecular and Genomic Medicine
    摘要: The Alu repetitive elements, which constitute 10% of human genome, may serve as bridges for genomic recombination. However, their roles in tumorigenesis remain to be elucidated. Caspase-activated DNase (CAD), whose gene (hCAD) is mapped at chromosome 1p36, a region frequently displaying hemizygote deletion in many human cancers, is the key enzyme for nucleosome fragmentation during apoptosis. Recently, we detected many aberrant mRNAs for hCAD in many human hepatoma cells. To elucidate the genetic basis leading to the mRNA aberration, we used PCR-based chromosome walking to clone the corresponding genomic DNA identifying a novel Alu/Alu homologous recombination/ deletion within hCAD in HepG2 and Hep3B cells. We then detected similar recombination events in 13 out of the 20 hepatoma tissues and in eight of the para-cancerous cirrhotic livers. The recombination was inclined to occur in males (P = 0.031) and had marginal association with high-grade hepatoma (P = 0.070) and tumor recurrence (P = 0.070). The recombination caused exon-3 deletion, which in turn led to exon-3 skipping or replacement with a partial Alu-sequence, and consequential C-truncation of CAD. Our findings of high frequency of Alu-mediated hCAD deletion in human hepatoma not only underscore the implication of hCAD in hepatocarcinogenesis, but also highlight the potential roles of human repetitive sequences in mediating genome instability in human cancers.
    关键词: Biochemistry & Molecular Biology;Oncology;Cell Biology;Genetics & Heredity
    日期: 2005-09
    關聯: Oncogene. 2005 Sep;24(43):6584-6589.
    Link to: http://dx.doi.org/10.1038/sj.onc.1208803
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000232204100012
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=26944433502
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