title: Tumour class prediction and discovery by microarray-based DNA methylation analysis.
abstract: Aberrant DNA methylation of CpG sites is among the earliest and most frequent alterations in cancer. Several studies suggest that aberrant methylation occurs in a tumour type-specific manner. However, large-scale analysis of candidate genes has so far been hampered by the lack of high throughput assays for methylation detection. We have developed the first microarray-based technique which allows genome-wide assessment of selected CpG dinucleotides as well as quantification of methylation at each site. Several hundred CpG sites were screened in 76 samples from four different human tumour types and corresponding healthy controls. Discriminative CpG dinucleotides were identified for different tissue type distinctions and used to predict the tumour class of as yet unknown samples with high accuracy using machine learning techniques. Some CpG dinucleotides correlate with progression to malignancy, whereas others are methylated in a tissue-specific manner independent of malignancy. Our results demonstrate that genome-wide analysis of methylation patterns combined with supervised and unsupervised machine learning techniques constitute a powerful novel tool to classify human cancers.
authors.affiliation: Information Sciences, Biomedical Research and Development, Epigenomics AG, Berlin, Germany.
authors.forename: Péter
authors.initials: P
authors.lastname: Adorján
authors.forename: Jürgen
authors.initials: J
authors.lastname: Distler
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lipscher
authors.forename: Fabian
authors.initials: F
authors.lastname: Model
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.forename: Cécile
authors.initials: C
authors.lastname: Pelet
authors.forename: Aron
authors.initials: A
authors.lastname: Braun
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Florl
authors.forename: David
authors.initials: D
authors.lastname: Gütig
authors.forename: Gabi
authors.initials: G
authors.lastname: Grabs
authors.forename: André
authors.initials: A
authors.lastname: Howe
authors.forename: Mischo
authors.initials: M
authors.lastname: Kursar
authors.forename: Ralf
authors.initials: R
authors.lastname: Lesche
authors.forename: Erik
authors.initials: E
authors.lastname: Leu
authors.forename: André
authors.initials: A
authors.lastname: Lewin
authors.forename: Sabine
authors.initials: S
authors.lastname: Maier
authors.forename: Volker
authors.initials: V
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Otto
authors.forename: Christian
authors.initials: C
authors.lastname: Scholz
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schulz
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Seifert
authors.forename: Ina
authors.initials: I
authors.lastname: Schwope
authors.forename: Heike
authors.initials: H
authors.lastname: Ziebarth
authors.forename: Kurt
authors.initials: K
authors.lastname: Berlin
authors.forename: Christian
authors.initials: C
authors.lastname: Piepenbrock
authors.forename: Alexander
authors.initials: A
authors.lastname: Olek
mesh_terms: D000465:Algorithms; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000145:classification* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm