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Article: Methylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers

TitleMethylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancers
Authors
Keywordsbiomarker
lung cancer
methylation
screening
TCF21
Issue Date2011
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741
Citation
Cancer, 2011, v. 117 n. 3, p. 606-617 How to Cite?
AbstractBackground: The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, further characterization of the stages and types of nonsmall cell lung cancer (NSCLC) that are hypermethylated and the frequency of hypermethylation and associated "second hits" were assessed. Methods: TCF21 promoter hypermethylation in 105 NSCLC including various stages and histologies in smokers and nonsmokers was determined. In addition, TCF21 loss of heterozygosity and mutational status were examined. Twenty-two cancer cell lines from varied tissue origins were also assayed. The NSCLC results were validated and expanded by examining TCF21 immunohistochemical expression on a tissue microarray containing 300 NSCLC cases. Results: Overall, 81% of NSCLC samples showed TCF21 promoter hypermethylation, and 84% showed decreased TCF21 protein expression. Multivariate analysis showed that TCF21 expression, although below normal in both histologies, was lower in adenocarcinoma than in squamous cell carcinoma and was not independently correlated with sex, smoking, and EGFR mutation status or with clinical outcome. Cell lines from other cancer types also showed frequent TCF21 promoter hypermethylation. Conclusions: Hypermethylation and decreased expression of TCF21 were tumor specific and very frequent in all NSCLCs, even early-stage disease, thus making TCF21 a potential candidate methylation biomarker for early-stage NSCLC screening. TCF21 hypermethylation in a variety of tumor cell lines suggests it may also be a valuable methylation biomarker in other tumor types. © 2010 American Cancer Society.
Persistent Identifierhttp://hdl.handle.net/10722/146598
ISSN
2015 Impact Factor: 5.649
2015 SCImago Journal Rankings: 3.188
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Kleberg Foundation
DoDW81XWH-05-2-0027
NIH-NCIP01 CA34936
Funding Information:

Supported in part by the Kleberg Foundation, DoD W81XWH-05-2-0027, and NIH-NCI P01 CA34936 (to R.K.). These agencies had no involvement in the study design; in the collection, analysis, and interpretation of data; in writing of the manuscript; and in the decision to submit the manuscript for publication.

References

 

DC FieldValueLanguage
dc.contributor.authorRichards, KLen_HK
dc.contributor.authorZhang, Ben_HK
dc.contributor.authorSun, Men_HK
dc.contributor.authorDong, Wen_HK
dc.contributor.authorChurchill, Jen_HK
dc.contributor.authorBachinski, LLen_HK
dc.contributor.authorWilson, CDen_HK
dc.contributor.authorBaggerly, KAen_HK
dc.contributor.authorYin, Gen_HK
dc.contributor.authorHayes, DNen_HK
dc.contributor.authorWistuba, IIen_HK
dc.contributor.authorKrahe, Ren_HK
dc.date.accessioned2012-05-02T08:37:19Z-
dc.date.available2012-05-02T08:37:19Z-
dc.date.issued2011en_HK
dc.identifier.citationCancer, 2011, v. 117 n. 3, p. 606-617en_HK
dc.identifier.issn0008-543Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/146598-
dc.description.abstractBackground: The transcription factor TCF21 is involved in mesenchymal-to-epithelial differentiation and was shown to be aberrantly hypermethylated in lung and head and neck cancers. Because of its reported high frequency of hypermethylation in lung cancer, further characterization of the stages and types of nonsmall cell lung cancer (NSCLC) that are hypermethylated and the frequency of hypermethylation and associated "second hits" were assessed. Methods: TCF21 promoter hypermethylation in 105 NSCLC including various stages and histologies in smokers and nonsmokers was determined. In addition, TCF21 loss of heterozygosity and mutational status were examined. Twenty-two cancer cell lines from varied tissue origins were also assayed. The NSCLC results were validated and expanded by examining TCF21 immunohistochemical expression on a tissue microarray containing 300 NSCLC cases. Results: Overall, 81% of NSCLC samples showed TCF21 promoter hypermethylation, and 84% showed decreased TCF21 protein expression. Multivariate analysis showed that TCF21 expression, although below normal in both histologies, was lower in adenocarcinoma than in squamous cell carcinoma and was not independently correlated with sex, smoking, and EGFR mutation status or with clinical outcome. Cell lines from other cancer types also showed frequent TCF21 promoter hypermethylation. Conclusions: Hypermethylation and decreased expression of TCF21 were tumor specific and very frequent in all NSCLCs, even early-stage disease, thus making TCF21 a potential candidate methylation biomarker for early-stage NSCLC screening. TCF21 hypermethylation in a variety of tumor cell lines suggests it may also be a valuable methylation biomarker in other tumor types. © 2010 American Cancer Society.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/28741en_HK
dc.relation.ispartofCanceren_HK
dc.subjectbiomarkeren_HK
dc.subjectlung canceren_HK
dc.subjectmethylationen_HK
dc.subjectscreeningen_HK
dc.subjectTCF21en_HK
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors - Genetics - Metabolismen_US
dc.subject.meshCarcinoma, Non-Small-Cell Lung - Geneticsen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshLung Neoplasms - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshTumor Markers, Biological - Geneticsen_US
dc.titleMethylation of the candidate biomarker TCF21 is very frequent across a spectrum of early-stage nonsmall cell lung cancersen_HK
dc.typeArticleen_HK
dc.identifier.emailYin, G: gyin@hku.hken_HK
dc.identifier.authorityYin, G=rp00831en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/cncr.25472en_HK
dc.identifier.pmid20945327en_HK
dc.identifier.pmcidPMC3023841-
dc.identifier.scopuseid_2-s2.0-79251487851en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79251487851&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume117en_HK
dc.identifier.issue3en_HK
dc.identifier.spage606en_HK
dc.identifier.epage617en_HK
dc.identifier.isiWOS:000286433300026-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRichards, KL=7202474246en_HK
dc.identifier.scopusauthoridZhang, B=35207378100en_HK
dc.identifier.scopusauthoridSun, M=14833715200en_HK
dc.identifier.scopusauthoridDong, W=16063096500en_HK
dc.identifier.scopusauthoridChurchill, J=37080429400en_HK
dc.identifier.scopusauthoridBachinski, LL=18033286300en_HK
dc.identifier.scopusauthoridWilson, CD=7404894802en_HK
dc.identifier.scopusauthoridBaggerly, KA=6603944321en_HK
dc.identifier.scopusauthoridYin, G=8725807500en_HK
dc.identifier.scopusauthoridHayes, DN=9737310200en_HK
dc.identifier.scopusauthoridWistuba, II=35375776900en_HK
dc.identifier.scopusauthoridKrahe, R=7003685358en_HK

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