title: Aberrant CpG-island methylation has non-random and tumour-type-specific patterns.
abstract: CpG islands frequently contain gene promoters or exons and are usually unmethylated in normal cells. Methylation of CpG islands is associated with delayed replication, condensed chromatin and inhibition of transcription initiation. The investigation of aberrant CpG-island methylation in human cancer has primarily taken a candidate gene approach, and has focused on less than 15 of the estimated 45,000 CpG islands in the genome. Here we report a global analysis of the methylation status of 1,184 unselected CpG islands in each of 98 primary human tumours using restriction landmark genomic scanning (RLGS). We estimate that an average of 600 CpG islands (range of 0 to 4,500) of the 45,000 in the genome were aberrantly methylated in the tumours, including early stage tumours. We identified patterns of CpG-island methylation that were shared within each tumour type, together with patterns and targets that displayed distinct tumour-type specificity. The expression of many of these genes was reactivated by experimental demethylation in cultured tumour cells. Thus, the methylation of particular subsets of CpG islands may have consequences for specific tumour types.
authors.affiliation: [1] Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla, California, USA. jcostello@cc.ucsf.edu
authors.forename: J F
authors.initials: JF
authors.lastname: Costello
authors.forename: M C
authors.initials: MC
authors.lastname: Frühwald
authors.forename: D J
authors.initials: DJ
authors.lastname: Smiraglia
authors.forename: L J
authors.initials: LJ
authors.lastname: Rush
authors.forename: G P
authors.initials: GP
authors.lastname: Robertson
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: F A
authors.initials: FA
authors.lastname: Wright
authors.forename: J D
authors.initials: JD
authors.lastname: Feramisco
authors.forename: P
authors.initials: P
authors.lastname: Peltomäki
authors.forename: J C
authors.initials: JC
authors.lastname: Lang
authors.forename: D E
authors.initials: DE
authors.lastname: Schuller
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: M A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: A
authors.initials: A
authors.lastname: Yates
authors.forename: R
authors.initials: R
authors.lastname: Nishikawa
authors.forename: H
authors.initials: H
authors.lastname: Su Huang
authors.forename: N J
authors.initials: NJ
authors.lastname: Petrelli
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: M S
authors.initials: MS
authors.lastname: O'Dorisio
authors.forename: W A
authors.initials: WA
authors.lastname: Held
authors.forename: W K
authors.initials: WK
authors.lastname: Cavenee
authors.forename: C
authors.initials: C
authors.lastname: Plass
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000032:analysis* / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide