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
  • Basic View
  • Metadata View
  • XML View
TitleA genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies
 
AuthorsShames, DS1 7
Girard, L1 7
Gao, B1 7
Sato, M7
Lewis, CM1
Shivapurkar, N1 7
Jiang, A8
Perou, CM9
Kim, YH5
Pollack, JR5
Fong, KM2
Lam, CL4
Wong, M4
Shyr, Y8
Nanda, R6
Olopade, OI6
Gerald, W3
Euhus, DM1
Shay, JW7
Gazdar, AF1 7
Minna, JD7 1
 
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
 
CitationPlos Medicine, 2006, v. 3 n. 12, p. 2244-2263 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pmed.0030486
 
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.
 
ISSN1549-1277
 
DOIhttp://dx.doi.org/10.1371/journal.pmed.0030486
 
PubMed Central IDPMC1716188
 
ISI Accession Number IDWOS:000243482500018
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorShames, DS
 
dc.contributor.authorGirard, L
 
dc.contributor.authorGao, B
 
dc.contributor.authorSato, M
 
dc.contributor.authorLewis, CM
 
dc.contributor.authorShivapurkar, N
 
dc.contributor.authorJiang, A
 
dc.contributor.authorPerou, CM
 
dc.contributor.authorKim, YH
 
dc.contributor.authorPollack, JR
 
dc.contributor.authorFong, KM
 
dc.contributor.authorLam, CL
 
dc.contributor.authorWong, M
 
dc.contributor.authorShyr, Y
 
dc.contributor.authorNanda, R
 
dc.contributor.authorOlopade, OI
 
dc.contributor.authorGerald, W
 
dc.contributor.authorEuhus, DM
 
dc.contributor.authorShay, JW
 
dc.contributor.authorGazdar, AF
 
dc.contributor.authorMinna, JD
 
dc.date.accessioned2010-09-06T09:47:57Z
 
dc.date.available2010-09-06T09:47:57Z
 
dc.date.issued2006
 
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.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos Medicine, 2006, v. 3 n. 12, p. 2244-2263 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pmed.0030486
 
dc.identifier.citeulike1288583
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pmed.0030486
 
dc.identifier.epage2263
 
dc.identifier.hkuros195651
 
dc.identifier.hkuros134761
 
dc.identifier.isiWOS:000243482500018
 
dc.identifier.issn1549-1277
 
dc.identifier.issue12
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC1716188
 
dc.identifier.pmid17194187
 
dc.identifier.scopuseid_2-s2.0-33845926895
 
dc.identifier.spage2244
 
dc.identifier.urihttp://hdl.handle.net/10722/88784
 
dc.identifier.volume3
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&issn=1549-1676
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS Medicine
 
dc.relation.referencesReferences in Scopus
 
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 malignancies
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Shames, DS</contributor.author>
<contributor.author>Girard, L</contributor.author>
<contributor.author>Gao, B</contributor.author>
<contributor.author>Sato, M</contributor.author>
<contributor.author>Lewis, CM</contributor.author>
<contributor.author>Shivapurkar, N</contributor.author>
<contributor.author>Jiang, A</contributor.author>
<contributor.author>Perou, CM</contributor.author>
<contributor.author>Kim, YH</contributor.author>
<contributor.author>Pollack, JR</contributor.author>
<contributor.author>Fong, KM</contributor.author>
<contributor.author>Lam, CL</contributor.author>
<contributor.author>Wong, M</contributor.author>
<contributor.author>Shyr, Y</contributor.author>
<contributor.author>Nanda, R</contributor.author>
<contributor.author>Olopade, OI</contributor.author>
<contributor.author>Gerald, W</contributor.author>
<contributor.author>Euhus, DM</contributor.author>
<contributor.author>Shay, JW</contributor.author>
<contributor.author>Gazdar, AF</contributor.author>
<contributor.author>Minna, JD</contributor.author>
<date.accessioned>2010-09-06T09:47:57Z</date.accessioned>
<date.available>2010-09-06T09:47:57Z</date.available>
<date.issued>2006</date.issued>
<identifier.citation>Plos Medicine, 2006, v. 3 n. 12, p. 2244-2263</identifier.citation>
<identifier.issn>1549-1277</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/88784</identifier.uri>
<description.abstract>Background: Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The &quot;rules&quot; 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&#8242; CpG islands, are induced from undetectable levels by 5-aza-2&#8242;-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. &#169; 2006 Shames et al.</description.abstract>
<language>eng</language>
<publisher>Public Library of Science. The Journal&apos;s web site is located at http://medicine.plosjournals.org/perlserv/?request=index-html&amp;issn=1549-1676</publisher>
<relation.ispartof>PLoS Medicine</relation.ispartof>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<subject.mesh>Carcinoma, Adenosquamous - genetics</subject.mesh>
<subject.mesh>DNA Methylation</subject.mesh>
<subject.mesh>Gene Expression Profiling - methods</subject.mesh>
<subject.mesh>Lung Neoplasms - genetics</subject.mesh>
<subject.mesh>Promoter Regions, Genetic - genetics</subject.mesh>
<title>A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=1549-1277&amp;volume=3&amp;issue=12, article no. e486&amp;spage=2244&amp;epage=2263&amp;date=2006&amp;atitle=A+genome-wide+screen+for+promoter+methylation+in+lung+cancer+identifies+novel+methylation+markers+for+multiple+malignancies</identifier.openurl>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1371/journal.pmed.0030486</identifier.doi>
<identifier.pmid>17194187</identifier.pmid>
<identifier.pmcid>PMC1716188</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-33845926895</identifier.scopus>
<identifier.hkuros>195651</identifier.hkuros>
<identifier.hkuros>134761</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-33845926895&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>3</identifier.volume>
<identifier.issue>12</identifier.issue>
<identifier.spage>2244</identifier.spage>
<identifier.epage>2263</identifier.epage>
<identifier.isi>WOS:000243482500018</identifier.isi>
<publisher.place>United States</publisher.place>
<identifier.citeulike>1288583</identifier.citeulike>
<bitstream.url>http://hub.hku.hk/bitstream/10722/88784/1/pmed.0030486.pdf</bitstream.url>
</item>
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