Article: OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation
| Title | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Cui, Y9 Ying, Y9 Van Hasselt, A9 Ng, KM9 Yu, J9 Zhang, Q9 Jin, J6 Liu, D3 Rhim, JS4 Rha, SY2 Loyo, M7 Chan, ATC9 Srivastava, G1 Tsao, GSW1 Sellar, GC5 8 Sung, JJY9 Sidransky, D7 Tao, Q3 9 | ||||||
| Issue Date | 2008 | ||||||
| Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| Citation | Plos One, 2008, v. 3 n. 8 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0002990 | ||||||
| Abstract | Background: 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. | ||||||
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| DOI | http://dx.doi.org/10.1371/journal.pone.0002990 | ||||||
| ISI Accession Number ID | WOS:000264420900016
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. | ||||||
| References | References in Scopus |
| dc.contributor.author | Cui, Y | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Ying, Y | ||||||
| dc.contributor.author | Van Hasselt, A | ||||||
| dc.contributor.author | Ng, KM | ||||||
| dc.contributor.author | Yu, J | ||||||
| dc.contributor.author | Zhang, Q | ||||||
| dc.contributor.author | Jin, J | ||||||
| dc.contributor.author | Liu, D | ||||||
| dc.contributor.author | Rhim, JS | ||||||
| dc.contributor.author | Rha, SY | ||||||
| dc.contributor.author | Loyo, M | ||||||
| dc.contributor.author | Chan, ATC | ||||||
| dc.contributor.author | Srivastava, G | ||||||
| dc.contributor.author | Tsao, GSW | ||||||
| dc.contributor.author | Sellar, GC | ||||||
| dc.contributor.author | Sung, JJY | ||||||
| dc.contributor.author | Sidransky, D | ||||||
| dc.contributor.author | Tao, Q | ||||||
| dc.date.accessioned | 2010-05-31T03:25:22Z | ||||||
| dc.date.available | 2010-05-31T03:25:22Z | ||||||
| dc.date.issued | 2008 | ||||||
| dc.description.abstract | Background: 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.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Plos One, 2008, v. 3 n. 8 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0002990 | ||||||
| dc.identifier.citeulike | 10379631 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0002990 | ||||||
| dc.identifier.hkuros | 150709 | ||||||
| dc.identifier.isi | WOS:000264420900016
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.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| dc.identifier.issue | 8 | ||||||
| dc.identifier.scopus | eid_2-s2.0-52049115449 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/58183 | ||||||
| dc.identifier.volume | 3 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | PLoS ONE | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.title | OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Yonsei University College of Medicine
- Johns Hopkins Singapore
- Uniformed Services University of the Health Sciences
- Wyeth Laboratory, Maidenhead
- Peking University
- The Johns Hopkins School of Medicine
- University of Edinburgh
- Chinese University of Hong Kong