Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors

Mi Yi Joo, Hsing Chen Tsai, Sabine C. Glöckner, Steven Lin, Joyce E. Ohm, Hari Easwaran, C. David James, Joseph F. Costello, Gregory Riggins, Charles G. Eberhart, John Laterra, Angelo L. Vescovi, Nita Ahuja, James G. Herman, Kornel E. Schuebel, Stephen B. Baylin

Research output: Contribution to journalArticle

Abstract

Much recent effort has focused on identifying and characterizing cellular markers that distinguish tumor propagating cells (TPC) from more differentiated progeny. We report here an unusual promoter DNA methylation pattern for one such marker, the cell surface antigen CD133 (Prominin 1). This protein has been extensively used to enrich putative cancer propagating stem-like cell populations in epithelial tumors and, especially, glioblastomas. We find that, within individual cell lines of cultured colon cancers and glioblastomas, the promoter CpG island of CD133 is DNA methylate d, primarily, in cells with absent or low expression of the marker protein, whereas lack of such methylation is evident in purely CD133+ cells. Differential histone modification marks of active versus repressed genes accompany these DNA methylation changes. This heterogeneous CpG island DNA methylation status in the tumors is unusual in that other DNA hypermethylate d genes tested in such cultures preserve their methylation patterns between separated CD133+ and CD133- cell populations. Furthermore, the CD133 DNA methylation seems to constitute an abnormal promoter signature because it is not found in normal brain and colon but only in cultured and primary tumors. Thus, the DNA methyl ation is imposed on the transition between the active versus repressed transcription state for CD133 only in tumors. Our findings provide additional insight for the dynamics of aberrant DNA methylation associated with aberrant gene silencing in human tumors.

Original languageEnglish
Pages (from-to)8094-8103
Number of pages10
JournalCancer Research
Volume68
Issue number19
DOIs
Publication statusPublished - Oct 1 2008

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Joo, M. Y., Tsai, H. C., Glöckner, S. C., Lin, S., Ohm, J. E., Easwaran, H., James, C. D., Costello, J. F., Riggins, G., Eberhart, C. G., Laterra, J., Vescovi, A. L., Ahuja, N., Herman, J. G., Schuebel, K. E., & Baylin, S. B. (2008). Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. Cancer Research, 68(19), 8094-8103. https://doi.org/10.1158/0008-5472.CAN-07-6208