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. ©2008 American Association for Cancer Research.

Yi, J., Tsai, H., Glöckner, S., Lin, S., Ohm, J., Easwaran, H., et al. (2008). Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. CANCER RESEARCH, 68(19), 8094-8103 [10.1158/0008-5472.CAN-07-6208].

Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors

VESCOVI, ANGELO LUIGI;
2008

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. ©2008 American Association for Cancer Research.
Articolo in rivista - Articolo scientifico
CD133 glioblastoma tumors
English
2008
68
19
8094
8103
none
Yi, J., Tsai, H., Glöckner, S., Lin, S., Ohm, J., Easwaran, H., et al. (2008). Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors. CANCER RESEARCH, 68(19), 8094-8103 [10.1158/0008-5472.CAN-07-6208].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/53124
Citazioni
  • Scopus 136
  • ???jsp.display-item.citation.isi??? 120
Social impact