title: Abnormal DNA methylation of CD133 in colorectal and glioblastoma tumors.
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 methylated, 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 hypermethylated 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 methylation 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.
authors.affiliation: Cancer Biology Division, Johns Hopkins Kimmel Cancer Center, USA.
authors.forename: Joo Mi
authors.initials: JM
authors.lastname: Yi
authors.forename: Hsing-Chen
authors.initials: HC
authors.lastname: Tsai
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Glöckner
authors.forename: Steven
authors.initials: S
authors.lastname: Lin
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Ohm
authors.forename: Hari
authors.initials: H
authors.lastname: Easwaran
authors.forename: C David
authors.initials: CD
authors.lastname: James
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
authors.forename: Gregory
authors.initials: G
authors.lastname: Riggins
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.forename: John
authors.initials: J
authors.lastname: Laterra
authors.forename: Angelo L
authors.initials: AL
authors.lastname: Vescovi
authors.forename: Nita
authors.initials: N
authors.lastname: Ahuja
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.forename: Kornel E
authors.initials: KE
authors.lastname: Schuebel
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001374:Azacitidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D018938:Caco-2 Cells; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D000077209:Decitabine; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine