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 journalArticlepeer-review

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation'. Together they form a unique fingerprint.

Cite this