File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Predictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting
  • Basic View
  • Metadata View
  • XML View
TitlePredictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting
 
AuthorsLamb, JR2
Zhang, C2
Xie, T2
Wang, K2
Zhang, B2
Hao, K2
Chudin, E2
Fraser, HB2
Millstein, J2
Ferguson, M2
Suver, C2
Ivanovska, I2
Scott, M3
Philippar, U3
Bansal, D3
Zhang, Z2
Burchard, J2
Smith, R2
Greenawalt, D2
Cleary, M3
Derry, J2
Loboda, A3
Watters, J3
Poon, RTP1
Fan, ST1
Yeung, C1
Lee, NPY1
Guinney, J4
Molony, C2
Emilsson, V2
BuserDoepner, C3
Zhu, J2
Friend, S3
Mao, M2
Shaw, PM3
Dai, H2
Luk, JM1
Schadt, EE2
 
Issue Date2011
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2011, v. 6 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0020090
 
AbstractBackground: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.
 
ISSN1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0020090
 
PubMed Central IDPMC3130029
 
ISI Accession Number IDWOS:000292512000005
Funding AgencyGrant Number
Merck Co
Funding Information:

This work was entirely funded by Merck & Co and its wholly owned subsidiary Rosetta Inpharmatics, Inc. Many of the authors were or are Merck employees. The manuscript was reviewed by Merck and approved for release into the public domain without alteration. Other than this Rosetta Inpharmatics and Merck had no role in study design, data collection and analysis, or preparation of the manuscript.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLamb, JR
 
dc.contributor.authorZhang, C
 
dc.contributor.authorXie, T
 
dc.contributor.authorWang, K
 
dc.contributor.authorZhang, B
 
dc.contributor.authorHao, K
 
dc.contributor.authorChudin, E
 
dc.contributor.authorFraser, HB
 
dc.contributor.authorMillstein, J
 
dc.contributor.authorFerguson, M
 
dc.contributor.authorSuver, C
 
dc.contributor.authorIvanovska, I
 
dc.contributor.authorScott, M
 
dc.contributor.authorPhilippar, U
 
dc.contributor.authorBansal, D
 
dc.contributor.authorZhang, Z
 
dc.contributor.authorBurchard, J
 
dc.contributor.authorSmith, R
 
dc.contributor.authorGreenawalt, D
 
dc.contributor.authorCleary, M
 
dc.contributor.authorDerry, J
 
dc.contributor.authorLoboda, A
 
dc.contributor.authorWatters, J
 
dc.contributor.authorPoon, RTP
 
dc.contributor.authorFan, ST
 
dc.contributor.authorYeung, C
 
dc.contributor.authorLee, NPY
 
dc.contributor.authorGuinney, J
 
dc.contributor.authorMolony, C
 
dc.contributor.authorEmilsson, V
 
dc.contributor.authorBuserDoepner, C
 
dc.contributor.authorZhu, J
 
dc.contributor.authorFriend, S
 
dc.contributor.authorMao, M
 
dc.contributor.authorShaw, PM
 
dc.contributor.authorDai, H
 
dc.contributor.authorLuk, JM
 
dc.contributor.authorSchadt, EE
 
dc.date.accessioned2011-09-23T05:55:04Z
 
dc.date.available2011-09-23T05:55:04Z
 
dc.date.issued2011
 
dc.description.abstractBackground: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. © 2011 Lamb et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2011, v. 6 n. 7 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0020090
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0020090
 
dc.identifier.epagee20090
 
dc.identifier.hkuros192464
 
dc.identifier.isiWOS:000292512000005
Funding AgencyGrant Number
Merck Co
Funding Information:

This work was entirely funded by Merck & Co and its wholly owned subsidiary Rosetta Inpharmatics, Inc. Many of the authors were or are Merck employees. The manuscript was reviewed by Merck and approved for release into the public domain without alteration. Other than this Rosetta Inpharmatics and Merck had no role in study design, data collection and analysis, or preparation of the manuscript.

 
dc.identifier.issn1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
dc.identifier.issue7
 
dc.identifier.pmcidPMC3130029
 
dc.identifier.pmid21750698
 
dc.identifier.scopuseid_2-s2.0-79960000200
 
dc.identifier.spagee20090
 
dc.identifier.urihttp://hdl.handle.net/10722/139743
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCarcinoma, Hepatocellular - genetics
 
dc.subject.meshDNA Copy Number Variations
 
dc.subject.meshGene Expression Profiling
 
dc.subject.meshLiver - metabolism - pathology
 
dc.subject.meshLiver Neoplasms - genetics
 
dc.titlePredictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Lamb, JR</contributor.author>
<contributor.author>Zhang, C</contributor.author>
<contributor.author>Xie, T</contributor.author>
<contributor.author>Wang, K</contributor.author>
<contributor.author>Zhang, B</contributor.author>
<contributor.author>Hao, K</contributor.author>
<contributor.author>Chudin, E</contributor.author>
<contributor.author>Fraser, HB</contributor.author>
<contributor.author>Millstein, J</contributor.author>
<contributor.author>Ferguson, M</contributor.author>
<contributor.author>Suver, C</contributor.author>
<contributor.author>Ivanovska, I</contributor.author>
<contributor.author>Scott, M</contributor.author>
<contributor.author>Philippar, U</contributor.author>
<contributor.author>Bansal, D</contributor.author>
<contributor.author>Zhang, Z</contributor.author>
<contributor.author>Burchard, J</contributor.author>
<contributor.author>Smith, R</contributor.author>
<contributor.author>Greenawalt, D</contributor.author>
<contributor.author>Cleary, M</contributor.author>
<contributor.author>Derry, J</contributor.author>
<contributor.author>Loboda, A</contributor.author>
<contributor.author>Watters, J</contributor.author>
<contributor.author>Poon, RTP</contributor.author>
<contributor.author>Fan, ST</contributor.author>
<contributor.author>Yeung, C</contributor.author>
<contributor.author>Lee, NPY</contributor.author>
<contributor.author>Guinney, J</contributor.author>
<contributor.author>Molony, C</contributor.author>
<contributor.author>Emilsson, V</contributor.author>
<contributor.author>BuserDoepner, C</contributor.author>
<contributor.author>Zhu, J</contributor.author>
<contributor.author>Friend, S</contributor.author>
<contributor.author>Mao, M</contributor.author>
<contributor.author>Shaw, PM</contributor.author>
<contributor.author>Dai, H</contributor.author>
<contributor.author>Luk, JM</contributor.author>
<contributor.author>Schadt, EE</contributor.author>
<date.accessioned>2011-09-23T05:55:04Z</date.accessioned>
<date.available>2011-09-23T05:55:04Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Plos One, 2011, v. 6 n. 7</identifier.citation>
<identifier.issn>1932-6203</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/139743</identifier.uri>
<description.abstract>Background: In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings: Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ~250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance: This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. &#169; 2011 Lamb et al.</description.abstract>
<language>eng</language>
<publisher>Public Library of Science. The Journal&apos;s web site is located at http://www.plosone.org/home.action</publisher>
<relation.ispartof>PLoS ONE</relation.ispartof>
<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<subject.mesh>Carcinoma, Hepatocellular - genetics</subject.mesh>
<subject.mesh>DNA Copy Number Variations</subject.mesh>
<subject.mesh>Gene Expression Profiling</subject.mesh>
<subject.mesh>Liver - metabolism - pathology</subject.mesh>
<subject.mesh>Liver Neoplasms - genetics</subject.mesh>
<title>Predictive genes in adjacent normal tissue are preferentially altered by sCNV during tumorigenesis in liver cancer and may rate limiting</title>
<type>Article</type>
<description.nature>published_or_final_version</description.nature>
<identifier.doi>10.1371/journal.pone.0020090</identifier.doi>
<identifier.pmid>21750698</identifier.pmid>
<identifier.pmcid>PMC3130029</identifier.pmcid>
<identifier.scopus>eid_2-s2.0-79960000200</identifier.scopus>
<identifier.hkuros>192464</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-79960000200&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>6</identifier.volume>
<identifier.issue>7</identifier.issue>
<identifier.spage>e20090</identifier.spage>
<identifier.epage>e20090</identifier.epage>
<identifier.isi>WOS:000292512000005</identifier.isi>
<publisher.place>United States</publisher.place>
<bitstream.url>http://hub.hku.hk/bitstream/10722/139743/1/pone.0020090.pdf</bitstream.url>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Rosetta Inpharmatics LLC
  3. Merck &amp; Co.
  4. Fred Hutchinson Cancer Research Center