High-throughput methylation profiling by MCA coupled to CpG island microarray

Marcos R H Estécio, Pearlly S. Yan, Ashraf E K Ibrahim, Carmen S. Tellez, Lanlan Shen, Hui-ming Huang, Jean Pierre J Issa

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

An abnormal pattern of DNA methylation occurs at specific genes in almost all neoplasms. The lack of high-throughput methods with high specificity and sensitivity to detect changes in DNA methylation has limited its application for clinical profiling. Here we overcome this limitation and present an improved method to identify methylated genes genome-wide by hybridizing a CpG island microarray with amplicons obtained by the methylated CpG island amplification technique (MCAM). We validated this method in three cancer cell lines and 15 primary colorectal tumors, resulting in the discovery of hundreds of new methylated genes in cancer. The sensitivity and specificity of the method to detect hypermethylated loci were 88% and 96%, respectively, according to validation by bisulfite-PCR. Unsupervised hierarchical clustering segregated the tumors into the expected subgroups based on CpG island methylator phenotype classification. In summary, MCAM is a suitable technique to discover methylated genes and to profile methylation changes in clinical samples in a high-throughput fashion.

Original languageEnglish (US)
Pages (from-to)1529-1536
Number of pages8
JournalGenome Research
Volume17
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

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CpG Islands
Methylation
DNA Methylation
Genes
Sensitivity and Specificity
Neoplasms
Neoplasm Genes
Cluster Analysis
Colorectal Neoplasms
Genome
Phenotype
Cell Line
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Genetics

Cite this

Estécio, M. R. H., Yan, P. S., Ibrahim, A. E. K., Tellez, C. S., Shen, L., Huang, H., & Issa, J. P. J. (2007). High-throughput methylation profiling by MCA coupled to CpG island microarray. Genome Research, 17(10), 1529-1536. https://doi.org/10.1101/gr.6417007

High-throughput methylation profiling by MCA coupled to CpG island microarray. / Estécio, Marcos R H; Yan, Pearlly S.; Ibrahim, Ashraf E K; Tellez, Carmen S.; Shen, Lanlan; Huang, Hui-ming; Issa, Jean Pierre J.

In: Genome Research, Vol. 17, No. 10, 10.2007, p. 1529-1536.

Research output: Contribution to journalArticle

Estécio, MRH, Yan, PS, Ibrahim, AEK, Tellez, CS, Shen, L, Huang, H & Issa, JPJ 2007, 'High-throughput methylation profiling by MCA coupled to CpG island microarray', Genome Research, vol. 17, no. 10, pp. 1529-1536. https://doi.org/10.1101/gr.6417007
Estécio MRH, Yan PS, Ibrahim AEK, Tellez CS, Shen L, Huang H et al. High-throughput methylation profiling by MCA coupled to CpG island microarray. Genome Research. 2007 Oct;17(10):1529-1536. https://doi.org/10.1101/gr.6417007
Estécio, Marcos R H ; Yan, Pearlly S. ; Ibrahim, Ashraf E K ; Tellez, Carmen S. ; Shen, Lanlan ; Huang, Hui-ming ; Issa, Jean Pierre J. / High-throughput methylation profiling by MCA coupled to CpG island microarray. In: Genome Research. 2007 ; Vol. 17, No. 10. pp. 1529-1536.
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