title: A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in human colorectal cancer.
abstract: Altered promoter DNA methylation, one of the most important molecular alterations in cancer, is proposed to correlate with deregulation of DNA methyltransferases, although the molecular mechanisms implicated are still poorly understood. Here we show that the de novo DNA methyltransferase DNMT3B is frequently repressed in human colorectal cancer cell lines (CCL) and primary tumours by aberrant DNA hypermethylation of its distal promoter. At the epigenome level, DNMT3B promoter hypermethylation was associated with the hypomethylation of gene promoters usually hypermethylated in the healthy colon. Forced DNMT3B overexpression in cancer cells restored the methylation levels of these promoters in the healthy colon. Our results show a new molecular mechanism of aberrant DNMT3B regulation in colon cancer and suggest that its expression is associated with the methylation of constitutively hypermethylated promoters in the healthy colon.
authors.affiliation: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias, HUCA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Covadonga
authors.initials: C
authors.lastname: Huidobro
authors.forename: Rocío G
authors.initials: RG
authors.lastname: Urdinguio
authors.forename: Ramón María
authors.initials: RM
authors.lastname: Rodríguez
authors.forename: Cristina
authors.initials: C
authors.lastname: Mangas
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calvanese
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Camblor
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrero
authors.forename: Adolfo
authors.initials: A
authors.lastname: Parra-Blanco
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Alvaro J
authors.initials: AJ
authors.lastname: Obaya
authors.forename: Laura
authors.initials: L
authors.lastname: Suárez-Fernández
authors.forename: Aurora
authors.initials: A
authors.lastname: Astudillo
authors.forename: Henar
authors.initials: H
authors.lastname: Hernando
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernández
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014162:Transfection; D000097584:DNA Methyltransferase 3B
chemical_list: D001374:Azacitidine; D004248:DNA (Cytosine-5-)-Methyltransferases; D000077209:Decitabine; D004791:Enzyme Inhibitors; D000097584:DNA Methyltransferase 3B