Hypomethylated blocks are large continuous blocks of genomic regions that are hypomethylated and account for up to 95% of the methylation change in cancer. They have been recently discovered as a universal defining epigenetic alteration in solid tumors [1,2]. The blocks range between 5 kb and 10 Mbp (median at 28 kb) in size and cover more than half of the human genome. About 1/3 of the single copy gene transcription start sites (TSS) are located within the blocks. The blocks overlap significantly with heterochromatin regions including lamina associated domains (LADs) and large organized chromatin lysine modifications (LOCKs), suggesting a strong link between methylation alterations and chromatin structural changes in cancer. Compared to normal, the blocks are not only affected by overall hypomethylation in cancer, but also observed hypervariable in methylation among individual cancer samples. In fact, the blocks encompass the majority of the genes showing higher or extreme cross-sample gene expression variability in cancer. Taken together, in addition to the overall levels of methylation and gene expression, the variabilities of methylation and gene expression are just as or perhaps even more important features in cancer heterogeneity, progression and epigenetic destabilization.
Arraystar 4 x 180K Human Hypomethylated Block Array is specifically designed to study the blocks in human cancers. The array covers 7088 blocks which encompass 2554 protein coding genes, 8481 lncRNAs, and 463 miRNA genes. The microarray can be used to detect methylation changes, histone modifications and transcription factor binding of the protein-coding and lncRNA genes the blocks. By integrating gene expression data from Arraystar gene expression array profiling, the dynamics of methylation and the gene expression in cancer can be correlated and their biology analyzed.
Figure 1. The expression values for 26 hypervariable genes in cancer located within hypomethylated blocks, with cancer samples (red) showing large expressional variations compared to the normal samples (blue) .
1. Hansen, K. D., et al. (2011) Nat Genet 43 (8): 768-75.
2. Timp, W., et al. (2014) Genome Med 6 (8): 61.
• Cancer block methylation is a universal defining epigenetic alteration in solid tumors, accounting for more than 95% of the methylation change in cancers.
• Hypervariabilities of methylation and gene expression within the blocks are important features in cancer epigenetic instability, heterogeneity and progression.
• More than 7000 cancer blocks on the microarray, covering protein coding genes, long non-coding genes and microRNA genes.
• The microarray is used for MeDIP and ChIP profiling of methylation, histone modification, and transcription factor binding in the cancer blocks.
• Dual color channels for MeDIP and input DNA, achieving excellent sensitivity and specificity.