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

Yan Cui1, Ying Ying, Andrew van Hasselt

  • 1State Key Laboratory in Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, Chinese University of Hong Kong, Hong Kong, China.

Plos One
|August 21, 2008
PubMed
Abstract

Insights

We identified OPCML as a broad tumor suppressor gene. Its silencing by methylation is frequent in many cancers, impacting tumor growth and stress response.

Area of Science:

  • Epigenetics and Cancer Biology
  • Tumor Suppressor Gene Identification

Background:

  • CpG methylation-silenced tumor suppressor genes (TSGs) are key to tumorigenesis and serve as biomarkers.
  • Loss of heterozygosity at 11q25 is common in various tumors, including nasopharyngeal carcinoma (NPC).
  • OPCML, located at 11q25, was identified as a downregulated gene via digital expression subtraction.

Purpose of the Study:

  • To investigate the role of OPCML in tumorigenesis.
  • To determine the mechanism of OPCML downregulation.
  • To assess OPCML's potential as a tumor suppressor across multiple cancer types.

Main Methods:

  • Semi-quantitative RT-PCR to assess OPCML expression.
  • Multiplex differential DNA-PCR to detect homozygous deletions.
  • Promoter methylation analysis in various cancer cell lines and primary tumors.
  • Demethylation studies (pharmacological and genetic) to confirm epigenetic silencing.
  • Ectopic expression of OPCML in cancer cells.

Main Results:

  • Frequent OPCML silencing was observed in NPC and other common tumors, without homozygous deletions.
  • Promoter methylation of OPCML was detected in multiple carcinoma and lymphoma cell lines, but not in non-tumor cell lines.
  • Demethylation restored OPCML expression, confirming epigenetic silencing.
  • OPCML's stress-responsive function is impaired by promoter methylation.
  • Ectopic OPCML expression inhibited carcinoma cell growth.

Conclusions:

  • OPCML is identified as a broad tumor suppressor gene.
  • Frequent inactivation of OPCML by promoter methylation occurs across multiple malignancies.
  • OPCML methylation represents a significant epigenetic mechanism in cancer development.

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