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Article: Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers

TitleChromatid cohesion defects may underlie chromosome instability in human colorectal cancers
Authors
KeywordsCDC4
MRE11A
Somatic mutation
Issue Date2008
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 9, p. 3443-3448 How to Cite?
AbstractAlthough the majority of colorectal cancers exhibit chromosome instability (CIN), only a few genes that might cause this phenotype have been identified and no general mechanism underlying their function has emerged. To systematically identify somatic mutations in potential CIN genes in colorectal cancers, we determined the sequence of 102 human homologues of 96 yeast CIN genes known to function in various aspects of chromosome transmission fidelity. We identified 11 somatic mutations distributed among five genes in a panel that included 132 colorectal cancers. Remarkably, all but one of these 11 mutations were in the homologs of yeast genes that regulate sister chromatid cohesion. We then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells. Finally, we showed that down-regulation or genetic disruption of the two major candidate CIN genes identified in previous studies (MRE11A and CDC4) also resulted in abnormal sister chromatid cohesion in human cells. These results suggest that defective sister chromatid cohesion as a result of somatic mutations may represent a major cause of chromosome instability in human cancers. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/137033
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBarber, TDen_HK
dc.contributor.authorMcManus, Ken_HK
dc.contributor.authorYuen, KWYen_HK
dc.contributor.authorReis, Men_HK
dc.contributor.authorParmigiani, Gen_HK
dc.contributor.authorShen, Den_HK
dc.contributor.authorBarrett, Ien_HK
dc.contributor.authorNouhi, Yen_HK
dc.contributor.authorSpencer, Fen_HK
dc.contributor.authorMarkowitz, Sen_HK
dc.contributor.authorVelculescu, VEen_HK
dc.contributor.authorKinzler, KWen_HK
dc.contributor.authorVogelstein, Ben_HK
dc.contributor.authorLengauer, Cen_HK
dc.contributor.authorHieter, Pen_HK
dc.date.accessioned2011-07-29T02:14:45Z-
dc.date.available2011-07-29T02:14:45Z-
dc.date.issued2008en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 9, p. 3443-3448en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137033-
dc.description.abstractAlthough the majority of colorectal cancers exhibit chromosome instability (CIN), only a few genes that might cause this phenotype have been identified and no general mechanism underlying their function has emerged. To systematically identify somatic mutations in potential CIN genes in colorectal cancers, we determined the sequence of 102 human homologues of 96 yeast CIN genes known to function in various aspects of chromosome transmission fidelity. We identified 11 somatic mutations distributed among five genes in a panel that included 132 colorectal cancers. Remarkably, all but one of these 11 mutations were in the homologs of yeast genes that regulate sister chromatid cohesion. We then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells. Finally, we showed that down-regulation or genetic disruption of the two major candidate CIN genes identified in previous studies (MRE11A and CDC4) also resulted in abnormal sister chromatid cohesion in human cells. These results suggest that defective sister chromatid cohesion as a result of somatic mutations may represent a major cause of chromosome instability in human cancers. © 2008 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectCDC4en_HK
dc.subjectMRE11Aen_HK
dc.subjectSomatic mutationen_HK
dc.titleChromatid cohesion defects may underlie chromosome instability in human colorectal cancersen_HK
dc.typeArticleen_HK
dc.identifier.emailYuen, KWY: kwyyuen@hku.hken_HK
dc.identifier.authorityYuen, KWY=rp01512en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.0712384105en_HK
dc.identifier.pmid18299561-
dc.identifier.pmcidPMC2265152-
dc.identifier.scopuseid_2-s2.0-40849149557en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-40849149557&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume105en_HK
dc.identifier.issue9en_HK
dc.identifier.spage3443en_HK
dc.identifier.epage3448en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000253846500049-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBarber, TD=7102704248en_HK
dc.identifier.scopusauthoridMcManus, K=7005089031en_HK
dc.identifier.scopusauthoridYuen, KWY=8841935800en_HK
dc.identifier.scopusauthoridReis, M=7102676429en_HK
dc.identifier.scopusauthoridParmigiani, G=7003983915en_HK
dc.identifier.scopusauthoridShen, D=7401738411en_HK
dc.identifier.scopusauthoridBarrett, I=7003347381en_HK
dc.identifier.scopusauthoridNouhi, Y=24071730500en_HK
dc.identifier.scopusauthoridSpencer, F=7102173759en_HK
dc.identifier.scopusauthoridMarkowitz, S=7102347123en_HK
dc.identifier.scopusauthoridVelculescu, VE=7004537356en_HK
dc.identifier.scopusauthoridKinzler, KW=7102898858en_HK
dc.identifier.scopusauthoridVogelstein, B=36077704000en_HK
dc.identifier.scopusauthoridLengauer, C=7005943106en_HK
dc.identifier.scopusauthoridHieter, P=7006930573en_HK
dc.identifier.citeulike9472133-

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