RT Journal
A1 Bibikova, Marina
A1 Lin, Zhenwu
A1 Zhou, Lixin
A1 Chudin, Eugene
A1 Garcia, Eliza Wickham
A1 Wu, Bonnie
A1 Doucet, Dennis
A1 Thomas, Neal J.
A1 Wang, Yunhua
A1 Vollmer, Ekkehard
A1 Goldmann, Torsten
A1 Seifart, Carola
A1 Jiang, Wei
A1 Barker, David L.
A1 Chee, Mark S.
A1 Floros, Joanna
A1 Fan, Jian-Bing
T1 High-throughput DNA methylation profiling using universal bead arrays
JF Genome Research 
JO Genome Research 
YR 2006 
FD March 01 
VO 16 
IS 3 
SP 383 
OP 393 
DO 10.1101/gr.4410706 
UL http://genome.cshlp.org/content/16/3/383.abstract 
AB We have developed a high-throughput method for analyzing the methylation status of hundreds of preselected genes simultaneously and have applied it to the discovery of methylation signatures that distinguish normal from cancer tissue samples. Through an adaptation of the GoldenGate genotyping assay implemented on a BeadArray platform, the methylation state of 1536 specific CpG sites in 371 genes (one to nine CpG sites per gene) was measured in a single reaction by multiplexed genotyping of 200 ng of bisulfite-treated genomic DNA. The assay was used to obtain a quantitative measure of the methylation level at each CpG site. After validating the assay in cell lines and normal tissues, we analyzed a panel of lung cancer biopsy samples (N = 22) and identified a panel of methylation markers that distinguished lung adenocarcinomas from normal lung tissues with high specificity. These markers were validated in a second sample set (N = 24). These results demonstrate the effectiveness of the method for reliably profiling many CpG sites in parallel for the discovery of informative methylation markers. The technology should prove useful for DNA methylation analyses in large populations, with potential application to the classification and diagnosis of a broad range of cancers and other diseases.