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Article: Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: Whole-genome evidence from multiple cell lines

TitleDistinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: Whole-genome evidence from multiple cell lines
Authors
KeywordsAberrations
Genome
Human
Immortalization
Telomeres
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2004, v. 23 n. 56, p. 9090-9101 How to Cite?
AbstractChromosomal aberrations are common in cancers. However, the search for chromosomal aberrations leading to development of specific solid tumors has been severely hindered because the majority of solid tumors have complex chromosomal aberrations that differ within the same tumor types. A similar phenomenon exists in immortalized cell lines. The underlying mechanisms driving these diverse aberrations are largely unknown. Telomeres play crucial roles in protecting the integrity of eucaryotic chromosomes and maintaining genomic stability of human cells. Telomere lengths on individual chromosomes in normal human somatic cells are heterogeneous and undergo progressive shortening with aging process. In this study, for the first time, a molecular cytogenetic method using sequential telomere quantitative fluorescence in situ hybridization and spectral karyotyping on the same human metaphases was applied successfully to examine the dynamic profiles of individual telomere shortening and their relationship to chromosome aberrations in multiple human cell lines undergoing immortalization. Human ovarian surface epithelial cells and esophageal epithelial cells were immortalized by the expression of HPV16 E6 and E7, which drive cells to proliferate by inactivating p53 and Rb genes. In these cell lines, we consistently detected large-scale differences in telomere signal intensities not only among nonhomologous chromosome arms but also between some homologous chromosome arms. The cell lines derived from different donors had different profiles of critically short telomeres (lacking telomere signals). Strikingly, the different profiles of chromosomal structural aberrations in multiple immortalized cell lines were highly significantly associated with the distinct distributions of critically short telomeres in whole-genome. Since cellular immortalization is one of the hallmarks of cancer, our findings suggest that distinct profiles of critically short telomeres in different human individuals might play an essential role in determining the complex and individual-specific chromosomal structural aberrations in human solid tumors.
Persistent Identifierhttp://hdl.handle.net/10722/67372
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDeng, Wen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorLucas, JNen_HK
dc.contributor.authorSi, HXen_HK
dc.contributor.authorLeung, CSen_HK
dc.contributor.authorMak, Pen_HK
dc.contributor.authorWang, LDen_HK
dc.contributor.authorCheung, ALMen_HK
dc.date.accessioned2010-09-06T05:54:32Z-
dc.date.available2010-09-06T05:54:32Z-
dc.date.issued2004en_HK
dc.identifier.citationOncogene, 2004, v. 23 n. 56, p. 9090-9101en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67372-
dc.description.abstractChromosomal aberrations are common in cancers. However, the search for chromosomal aberrations leading to development of specific solid tumors has been severely hindered because the majority of solid tumors have complex chromosomal aberrations that differ within the same tumor types. A similar phenomenon exists in immortalized cell lines. The underlying mechanisms driving these diverse aberrations are largely unknown. Telomeres play crucial roles in protecting the integrity of eucaryotic chromosomes and maintaining genomic stability of human cells. Telomere lengths on individual chromosomes in normal human somatic cells are heterogeneous and undergo progressive shortening with aging process. In this study, for the first time, a molecular cytogenetic method using sequential telomere quantitative fluorescence in situ hybridization and spectral karyotyping on the same human metaphases was applied successfully to examine the dynamic profiles of individual telomere shortening and their relationship to chromosome aberrations in multiple human cell lines undergoing immortalization. Human ovarian surface epithelial cells and esophageal epithelial cells were immortalized by the expression of HPV16 E6 and E7, which drive cells to proliferate by inactivating p53 and Rb genes. In these cell lines, we consistently detected large-scale differences in telomere signal intensities not only among nonhomologous chromosome arms but also between some homologous chromosome arms. The cell lines derived from different donors had different profiles of critically short telomeres (lacking telomere signals). Strikingly, the different profiles of chromosomal structural aberrations in multiple immortalized cell lines were highly significantly associated with the distinct distributions of critically short telomeres in whole-genome. Since cellular immortalization is one of the hallmarks of cancer, our findings suggest that distinct profiles of critically short telomeres in different human individuals might play an essential role in determining the complex and individual-specific chromosomal structural aberrations in human solid tumors.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectAberrationsen_HK
dc.subjectGenomeen_HK
dc.subjectHumanen_HK
dc.subjectImmortalizationen_HK
dc.subjectTelomeresen_HK
dc.subject.meshCell Line, Transformeden_HK
dc.subject.meshChromosome Aberrationsen_HK
dc.subject.meshDNA Probesen_HK
dc.subject.meshGenome, Humanen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIn Situ Hybridization, Fluorescenceen_HK
dc.subject.meshKaryotypingen_HK
dc.subject.meshTelomereen_HK
dc.titleDistinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells: Whole-genome evidence from multiple cell linesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=23&spage=9090&epage=9101&date=2004&atitle=Distinct+profiles+of+critically+short+telomeres+are+a+key+determinant+of+different+chromosome+aberrations+in+immortalized+human+cells:+whole-genome+evidence+from+multiple+cell+linesen_HK
dc.identifier.emailDeng, W: wdeng@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_HK
dc.identifier.authorityDeng, W=rp01640en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityCheung, ALM=rp00332en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1208119en_HK
dc.identifier.pmid15489894en_HK
dc.identifier.scopuseid_2-s2.0-10944222118en_HK
dc.identifier.hkuros96581en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-10944222118&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue56en_HK
dc.identifier.spage9090en_HK
dc.identifier.epage9101en_HK
dc.identifier.isiWOS:000225492800010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridDeng, W=7202223673en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridLucas, JN=7402441937en_HK
dc.identifier.scopusauthoridSi, HX=36780537100en_HK
dc.identifier.scopusauthoridLeung, CS=36725510000en_HK
dc.identifier.scopusauthoridMak, P=7005044545en_HK
dc.identifier.scopusauthoridWang, LD=12242861000en_HK
dc.identifier.scopusauthoridCheung, ALM=7401806497en_HK

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