Methylation
CpG Island Microarrays Identify Gene Methylation in Lung Cancer
A review of Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
DNA methylation events serve as critical regulators of gene expression, with new evidence substantiating the correlation between methylation and human disease, such as cancer. Rauch and others at the Beckman Research Institute of the City of Hope (2007) used a methylated CpG island recovery assay (MIRA) in conjunction with Agilent’s Human CpG island microarrays to perform global, high-resolution analysis of HOX gene clusters in cell lines and primary lung tumors. The authors found that CpG islands within HOX clusters and near other homeobox genes are frequent methylation targets in lung cancer, and while not all HOX paralogues undergo this cancer-associated methylation, the HOXA cluster revealed DNA methylation markers for Stage 1 lung cancer. The results of this study "lend support to the hypothesis that a substantial fraction of genes methylated in human cancer are targets of the Polycomb complex, revealing the potential utility of DNA methylation markers for early disease diagnosis."
Figure 1. DNA methylation profiles of chromosomes 2, 7, 12, and 17 that carry the HOXA, HOXB, HOXC, and HOXD gene clusters.
MIRA-enriched fractions from A549 lung cancer cells and from NHBE cells were mixed and hybridized onto Agilent CpG island arrays. The ratio (fold difference) plotted indicates individual probe signals (blue diamonds) for hypermethylated CpG islands in A549 cells (A549/NHBE signal ratio). The numbers indicate selected areas of densely hypermethylated CpG island clusters for the genes indicated at the bottom.
Figure 2. Methylation of HOXA genes in normal lung tissue and matching stage 1 squamous cell carcinoma samples.
(A) Methylation differences between squamous cell carcinomas and matching normal pairs (pairs 1-4) were detected by COBRAs of HOX gene targets. T, tumor; N, normal tissues; -, control digestion with no BstUI; +, BstUI-digested samples. (B) Summary of the methylation status of promoters in the HOXA gene cluster.
Title: Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay
Journal: Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5527-32
Authors: Rauch T, Wang Z, Zhang X, Zhong X, Wu X, Lau SK, Kernstine KH, Riggs AD, Pfeifer GP
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