Tumour class prediction and discovery by microarray-based DNA methylation analysis.
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.
Adorján
Péter
P
Information Sciences, Biomedical Research and Development, Epigenomics AG, Berlin, Germany.
Distler
Jürgen
J
Lipscher
Evelyne
E
Model
Fabian
F
Müller
Jürgen
J
Pelet
Cécile
C
Braun
Aron
A
Florl
Andrea R
AR
Gütig
David
D
Grabs
Gabi
G
Howe
André
A
Kursar
Mischo
M
Lesche
Ralf
R
Leu
Erik
E
Lewin
André
A
Maier
Sabine
S
Müller
Volker
V
Otto
Thomas
T
Scholz
Christian
C
Schulz
Wolfgang A
WA
Seifert
Hans-Helge
HH
Schwope
Ina
I
Ziebarth
Heike
H
Berlin
Kurt
K
Piepenbrock
Christian
C
Olek
Alexander
A
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
D004273:DNA, Neoplasm