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    Homozygous deletions may be markers of nearby heterozygous mutations: the complex deletion at FRA16D in the HCT116 colon cancer cell line removes exons of WWOX

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    Authors
    Alsop, Amber E.
    Taylor, Karen J.
    Zhang, Jieqing
    Gabra, Hani
    Paige, Adam J.W.
    Edwards, Paul A.W.
    Affiliation
    University of Cambridge
    Issue Date
    2008-05
    
    Metadata
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    Abstract
    Homozygous deletions in cancer cells have been thought to harbor tumor suppressor genes. We show that the 25 and 50 kb homozygous deletions in WWOX in the colon cancer cell line HCT116 result from a complex set of heterozygous deletions, some of which overlap to give homozygous loss. One of the heterozygous deletions has removed exons 6-8 of one allele of WWOX, and there is also a third copy of the distal region of WWOX in an unbalanced translocation. The exon 6-8 deletion results in allele-specific expression of a deleted transcript, which seems likely to be the main biological consequence of the deletions, since similar transcripts are found in other tumors. We show that such a complex set of deletions could form in a single exchange event between two homologous chromosomes, so that the selective advantage of such rearrangements need not be within the homozygous deletion. We conclude that homozygous deletions can be markers of complex rearrangements that have targets outside the homozygous deletion itself and that the target of deletions in the FRA16D region is indeed WWOX, the common outcome being the removal of particular WWOX exons. This article contains supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
    Citation
    Alsop, A.E. et al (2008) 'Homozygous deletions may be markers of nearby heterozygous mutations: The complex deletion at FRA16D in the HCT116 colon cancer cell line removes exons of WWOX' Genes Chromosomes Cancer 47 (5):437-447
    Publisher
    Wiley-Blackwell
    Journal
    Genes, chromosomes & cancer
    URI
    http://hdl.handle.net/10547/228926
    DOI
    10.1002/gcc.20548
    PubMed ID
    18273838
    Additional Links
    http://www.ncbi.nlm.nih.gov/pubmed/18273838
    Type
    Article
    Language
    en
    ISSN
    1098-2264
    ae974a485f413a2113503eed53cd6c53
    10.1002/gcc.20548
    Scopus Count
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    Cell and Cryobiology Research Group

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