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Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
05:45

Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections

Published on: July 31, 2017

Epigenetic regulation of c-ROS receptor tyrosine kinase expression in malignant gliomas

Hyun Jung Jun1, Steve Woolfenden, Shanie Coven

  • 1Molecular Oncology Research Institute and Department of Neurosurgery, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts.

Cancer Research
|March 12, 2009
PubMed

Insights

Epigenetic changes, specifically c-ROS promoter hypomethylation, drive c-ROS expression in glioma. This discovery links c-ROS to glioma development and suggests caution with demethylating agents like 5-aza-2'-deoxycytidine in treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Proto-oncogene tyrosine kinase c-ROS is normally restricted during development.
  • c-ROS is frequently upregulated in glioma tumors.
  • c-ROS protein is detected in 25% of low-grade and 30% of malignant glioma samples.

Purpose of the Study:

  • Investigate the molecular basis for ectopic c-ROS expression in glioma.
  • Determine the role of c-ROS promoter methylation in its aberrant expression.
  • Explore the therapeutic implications of targeting c-ROS epigenetic regulation.

Main Methods:

  • Immunohistochemistry to detect c-ROS protein in glioma tissues.
  • Identification and characterization of the c-ROS gene promoter.
  • Bisulfite sequencing to analyze CpG island methylation status.
  • Treatment of c-ROS-negative cells with 5-aza-2 -deoxycytidine.

Main Results:

  • Ectopic c-ROS expression in glioma correlates with hypomethylation of a specific CpG island in its promoter.
  • Demethylation of the CpG island (-384 to -132 bp) is directly linked to c-ROS expression.
  • Treatment with 5-aza-2 -deoxycytidine activates c-ROS expression in previously negative cells.

Conclusions:

  • Epigenetic activation via c-ROS promoter demethylation is a key mechanism in glioma initiation and progression.
  • c-ROS promoter hypomethylation drives oncogenic function in glioma.
  • Clinical use of demethylating agents like 5-aza-2 -deoxycytidine for glioma treatment warrants careful consideration due to potential c-ROS activation.

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