File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies

TitleA genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies
Authors
Issue Date2006
PublisherPublic Library of Science. The Journal's web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&issn=1549-1676
Citation
Plos Medicine, 2006, v. 3 n. 12, p. 2244-2263 How to Cite?
Abstract
Background: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. Methods and Findings: In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5′ CpG islands, are induced from undetectable levels by 5-aza-2′-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. Conclusions: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention. © 2006 Shames et al.
Persistent Identifierhttp://hdl.handle.net/10722/88784
ISSN
PubMed Central ID
ISI Accession Number ID
References

 

Author Affiliations
  1. UT Southwestern Medical School
  2. University of Queensland
  3. Memorial Sloan-Kettering Cancer Center
  4. The University of Hong Kong
  5. Stanford University School of Medicine
  6. University of Chicago
  7. UT Southwestern Medical Center
  8. Vanderbilt University School of Medicine
  9. The University of North Carolina at Chapel Hill
DC FieldValueLanguage
dc.contributor.authorShames, DSen_HK
dc.contributor.authorGirard, Len_HK
dc.contributor.authorGao, Ben_HK
dc.contributor.authorSato, Men_HK
dc.contributor.authorLewis, CMen_HK
dc.contributor.authorShivapurkar, Nen_HK
dc.contributor.authorJiang, Aen_HK
dc.contributor.authorPerou, CMen_HK
dc.contributor.authorKim, YHen_HK
dc.contributor.authorPollack, JRen_HK
dc.contributor.authorFong, KMen_HK
dc.contributor.authorLam, CLDen_HK
dc.contributor.authorWong, Men_HK
dc.contributor.authorShyr, Yen_HK
dc.contributor.authorNanda, Ren_HK
dc.contributor.authorOlopade, OIen_HK
dc.contributor.authorGerald, Wen_HK
dc.contributor.authorEuhus, DMen_HK
dc.contributor.authorShay, JWen_HK
dc.contributor.authorGazdar, AFen_HK
dc.contributor.authorMinna, JDen_HK
dc.date.accessioned2010-09-06T09:47:57Z-
dc.date.available2010-09-06T09:47:57Z-
dc.date.issued2006en_HK
dc.identifier.citationPlos Medicine, 2006, v. 3 n. 12, p. 2244-2263en_HK
dc.identifier.issn1549-1277en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88784-
dc.description.abstractBackground: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. Methods and Findings: In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5′ CpG islands, are induced from undetectable levels by 5-aza-2′-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. Conclusions: By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention. © 2006 Shames et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&issn=1549-1676en_HK
dc.relation.ispartofPLoS Medicineen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshCarcinoma, Adenosquamous - genetics-
dc.subject.meshDNA Methylation-
dc.subject.meshGene Expression Profiling - methods-
dc.subject.meshLung Neoplasms - genetics-
dc.subject.meshPromoter Regions, Genetic - genetics-
dc.titleA genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignanciesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1549-1277&volume=3&issue=12, article no. e486&spage=2244&epage=2263&date=2006&atitle=A+genome-wide+screen+for+promoter+methylation+in+lung+cancer+identifies+novel+methylation+markers+for+multiple+malignanciesen_HK
dc.identifier.emailLam, CL:lamcl@hkucc.hku.hken_HK
dc.identifier.emailWong, M:mwpik@hkucc.hku.hken_HK
dc.identifier.authorityLam, CL=rp01345en_HK
dc.identifier.authorityWong, M=rp00348en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pmed.0030486en_HK
dc.identifier.pmid17194187-
dc.identifier.pmcidPMC1716188-
dc.identifier.scopuseid_2-s2.0-33845926895en_HK
dc.identifier.hkuros195651en_HK
dc.identifier.hkuros134761en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33845926895&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume3en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2244en_HK
dc.identifier.epage2263en_HK
dc.identifier.isiWOS:000243482500018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridShames, DS=34573130000en_HK
dc.identifier.scopusauthoridGirard, L=7101715512en_HK
dc.identifier.scopusauthoridGao, B=7201753543en_HK
dc.identifier.scopusauthoridSato, M=15074420800en_HK
dc.identifier.scopusauthoridLewis, CM=8054995900en_HK
dc.identifier.scopusauthoridShivapurkar, N=7004497157en_HK
dc.identifier.scopusauthoridJiang, A=15019507800en_HK
dc.identifier.scopusauthoridPerou, CM=7003834979en_HK
dc.identifier.scopusauthoridKim, YH=36068493700en_HK
dc.identifier.scopusauthoridPollack, JR=7101673347en_HK
dc.identifier.scopusauthoridFong, KM=7102709025en_HK
dc.identifier.scopusauthoridLam, CL=7201749615en_HK
dc.identifier.scopusauthoridWong, M=7403907887en_HK
dc.identifier.scopusauthoridShyr, Y=35431521800en_HK
dc.identifier.scopusauthoridNanda, R=8919136000en_HK
dc.identifier.scopusauthoridOlopade, OI=35392542100en_HK
dc.identifier.scopusauthoridGerald, W=7005991562en_HK
dc.identifier.scopusauthoridEuhus, DM=7004876935en_HK
dc.identifier.scopusauthoridShay, JW=7103373158en_HK
dc.identifier.scopusauthoridGazdar, AF=35372587300en_HK
dc.identifier.scopusauthoridMinna, JD=35380041500en_HK
dc.identifier.citeulike1288583-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats