OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation

Yan Cui, Ying Ying, Andrew Van Hasselt, Ka Man Ng, Jun Yu, Qian Zhang, Jie Jin, Dingxie Liu, Johng S. Rhim, Sun Young Rha, Myriam Loyo, Anthony T C Chan, Gopesh Srivastava, George S W Tsao, Grant C. Sellar, Joseph J Y Sung, David Sidransky, Qian Tao

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere2990
JournalPLoS One
Volume3
Issue number8
DOIs
StatePublished - Aug 20 2008
Externally publishedYes

Fingerprint

lymphoma
Epigenomics
epigenetics
carcinoma
Tumors
Lymphoma
inactivation
Methylation
Carcinoma
neoplasms
Cells
methylation
cell lines
Neoplasms
Cell Line
Genes
promoter regions
Hodgkin disease
Polymerase Chain Reaction
tumor suppressor genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. / Cui, Yan; Ying, Ying; Van Hasselt, Andrew; Ng, Ka Man; Yu, Jun; Zhang, Qian; Jin, Jie; Liu, Dingxie; Rhim, Johng S.; Rha, Sun Young; Loyo, Myriam; Chan, Anthony T C; Srivastava, Gopesh; Tsao, George S W; Sellar, Grant C.; Sung, Joseph J Y; Sidransky, David; Tao, Qian.

In: PLoS One, Vol. 3, No. 8, e2990, 20.08.2008.

Research output: Contribution to journalArticle

Cui, Y, Ying, Y, Van Hasselt, A, Ng, KM, Yu, J, Zhang, Q, Jin, J, Liu, D, Rhim, JS, Rha, SY, Loyo, M, Chan, ATC, Srivastava, G, Tsao, GSW, Sellar, GC, Sung, JJY, Sidransky, D & Tao, Q 2008, 'OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation', PLoS One, vol. 3, no. 8, e2990. https://doi.org/10.1371/journal.pone.0002990
Cui, Yan ; Ying, Ying ; Van Hasselt, Andrew ; Ng, Ka Man ; Yu, Jun ; Zhang, Qian ; Jin, Jie ; Liu, Dingxie ; Rhim, Johng S. ; Rha, Sun Young ; Loyo, Myriam ; Chan, Anthony T C ; Srivastava, Gopesh ; Tsao, George S W ; Sellar, Grant C. ; Sung, Joseph J Y ; Sidransky, David ; Tao, Qian. / OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation. In: PLoS One. 2008 ; Vol. 3, No. 8.
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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.",
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T1 - OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation

AU - Cui, Yan

AU - Ying, Ying

AU - Van Hasselt, Andrew

AU - Ng, Ka Man

AU - Yu, Jun

AU - Zhang, Qian

AU - Jin, Jie

AU - Liu, Dingxie

AU - Rhim, Johng S.

AU - Rha, Sun Young

AU - Loyo, Myriam

AU - Chan, Anthony T C

AU - Srivastava, Gopesh

AU - Tsao, George S W

AU - Sellar, Grant C.

AU - Sung, Joseph J Y

AU - Sidransky, David

AU - Tao, Qian

PY - 2008/8/20

Y1 - 2008/8/20

N2 - 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.

AB - 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.

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