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

2.50
Hdl Handle:
http://hdl.handle.net/10547/228926
Title:
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
Authors:
Alsop, Amber E.; Taylor, Karen J.; Zhang, Jieqing; Gabra, Hani; Paige, Adam J.W.; Edwards, Paul A.W.
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.
Affiliation:
University of Cambridge
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
Issue Date:
May-2008
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
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorAlsop, Amber E.en_GB
dc.contributor.authorTaylor, Karen J.en_GB
dc.contributor.authorZhang, Jieqingen_GB
dc.contributor.authorGabra, Hanien_GB
dc.contributor.authorPaige, Adam J.W.en_GB
dc.contributor.authorEdwards, Paul A.W.en_GB
dc.date.accessioned2012-06-14T11:35:32Zen
dc.date.available2012-06-14T11:35:32Zen
dc.date.issued2008-05en
dc.identifier.citationAlsop, 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):437-447en_GB
dc.identifier.issn1098-2264en
dc.identifier.pmid18273838en
dc.identifier.doi10.1002/gcc.20548en
dc.identifier.urihttp://hdl.handle.net/10547/228926en
dc.description.abstractHomozygous 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.en_GB
dc.language.isoenen
dc.publisherWiley-Blackwellen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/18273838en_GB
dc.subject.meshBase Sequenceen
dc.subject.meshCell Line, Tumoren
dc.subject.meshChromosomes, Human, Pair 16en
dc.subject.meshColonic Neoplasmsen
dc.subject.meshDNA Primersen
dc.subject.meshExonsen
dc.subject.meshGene Deletionen
dc.subject.meshHomozygoteen
dc.subject.meshHumansen
dc.subject.meshMutationen
dc.subject.meshOxidoreductasesen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshRNA, Messengeren
dc.subject.meshTranslocation, Geneticen
dc.subject.meshTumor Suppressor Proteinsen
dc.titleHomozygous deletions may be markers of nearby heterozygous mutations: the complex deletion at FRA16D in the HCT116 colon cancer cell line removes exons of WWOXen
dc.typeArticleen
dc.contributor.departmentUniversity of Cambridgeen_GB
dc.identifier.journalGenes, chromosomes & canceren_GB

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