Promoter DNA methylation of Oncostatin M receptor-β as a novel diagnostic and therapeutic marker in colon cancer

Myoung Sook Kim*, Joost Louwagie, Beatriz Carvalho, Jochim S. Terhaar sive Droste, Hannah Lui Park, Young Kwang Chae, Keishi Yamashita, Junwei Liu, Kimberly Laskie Ostrow, Shizhang Ling, Rafael Guerrero-Preston, Semra Demokan, Zubeyde Yalniz, Nejat Dalay, Gerrit A. Meijer, Wim Van Criekinge, David Sidransky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging "cancer methylome". In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-β (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/ 100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC.

Original languageEnglish (US)
Article numbere6555
JournalPloS one
Volume4
Issue number8
DOIs
StatePublished - Aug 7 2009

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Promoter DNA methylation of Oncostatin M receptor-β as a novel diagnostic and therapeutic marker in colon cancer'. Together they form a unique fingerprint.

Cite this