TY - JOUR 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 Y1 - 2006/03/01 JF - Genome Research JO - Genome Research SP - 383 EP - 393 DO - 10.1101/gr.4410706 VL - 16 IS - 3 UR - http://genome.cshlp.org/content/16/3/383.abstract N2 - 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. ER -