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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

  • Adam Paige
    ,
  • Amber E. Alsop
    ,
  • Karen J. Taylor
    ,
  • Jieqing Zhang
    ,
  • Hani Gabra
    ,
  • Paul A.W. Edwards
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 437-447

Journal (Volume, Issue Number)

Genes Chromosomes and Cancer (Volume 47, Issue 5)

Publication milestones

  • Published - 01/05/2008

Publication status

Published - 01/05/2008

ISSN

1045-2257

External Publication IDs

  • handle.net: 10547/228926
  • Scopus: 41349083952

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