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Article: OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation
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TitleOPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation
 
AuthorsCui, Y9
Ying, Y9
Van Hasselt, A9
Ng, KM9
Yu, J9
Zhang, Q9
Jin, J7
Liu, D3
Rhim, JS4
Rha, SY2
Loyo, M5
Chan, ATC9
Srivastava, G1
Tsao, GSW1
Sellar, GC8 6
Sung, JJY9
Sidransky, D5
Tao, Q9 3
 
Issue Date2008
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2008, v. 3 n. 8 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0002990
 
AbstractBackground: Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Methodology/Principal Findings: Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -indendent growth of carcinoma cells with endogenous silencing. Conlusions/Significance: Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. © 2008 Cui et al.
 
ISSN1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0002990
 
ISI Accession Number IDWOS:000264420900016
Funding AgencyGrant Number
Hong Kong RGC Central AllocationCA06/07.SC03
Chinese University of Hong Kong
Funding Information:

This project was supported by a Hong Kong RGC Central Allocation Grant (CA06/07.SC03 to QT) and a Chinese University of Hong Kong direct grant.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCui, Y
 
dc.contributor.authorYing, Y
 
dc.contributor.authorVan Hasselt, A
 
dc.contributor.authorNg, KM
 
dc.contributor.authorYu, J
 
dc.contributor.authorZhang, Q
 
dc.contributor.authorJin, J
 
dc.contributor.authorLiu, D
 
dc.contributor.authorRhim, JS
 
dc.contributor.authorRha, SY
 
dc.contributor.authorLoyo, M
 
dc.contributor.authorChan, ATC
 
dc.contributor.authorSrivastava, G
 
dc.contributor.authorTsao, GSW
 
dc.contributor.authorSellar, GC
 
dc.contributor.authorSung, JJY
 
dc.contributor.authorSidransky, D
 
dc.contributor.authorTao, Q
 
dc.date.accessioned2010-05-31T03:25:22Z
 
dc.date.available2010-05-31T03:25:22Z
 
dc.date.issued2008
 
dc.description.abstractBackground: Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Methodology/Principal Findings: Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -indendent growth of carcinoma cells with endogenous silencing. Conlusions/Significance: Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies. © 2008 Cui et al.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationPlos One, 2008, v. 3 n. 8 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0002990
 
dc.identifier.citeulike10379631
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0002990
 
dc.identifier.hkuros150709
 
dc.identifier.isiWOS:000264420900016
Funding AgencyGrant Number
Hong Kong RGC Central AllocationCA06/07.SC03
Chinese University of Hong Kong
Funding Information:

This project was supported by a Hong Kong RGC Central Allocation Grant (CA06/07.SC03 to QT) and a Chinese University of Hong Kong direct grant.

 
dc.identifier.issn1932-6203
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
 
dc.identifier.issue8
 
dc.identifier.pmid18714356
 
dc.identifier.scopuseid_2-s2.0-52049115449
 
dc.identifier.urihttp://hdl.handle.net/10722/58183
 
dc.identifier.volume3
 
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.titleOPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation
 
dc.typeArticle
 
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<contributor.author>Loyo, M</contributor.author>
<contributor.author>Chan, ATC</contributor.author>
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Author Affiliations
  1. The University of Hong Kong
  2. Yonsei University College of Medicine
  3. Johns Hopkins Singapore
  4. Uniformed Services University of the Health Sciences
  5. The Johns Hopkins School of Medicine
  6. Wyeth Laboratory, Maidenhead
  7. Peking University
  8. University of Edinburgh
  9. Chinese University of Hong Kong