Universal Blocks of Aberrant Methylation in Cancer Blocks

• Activity Number: 101
• Type: Invited
• Date/Time: Monday, August 4, 2014 : 8:30 AM to 10:20 AM
• Sponsor: WNAR
• Author(s): Rafael Irizarry*+
• Companies: Dana-Farber Cancer Institute
• Keywords: DNA methylation ; Microarrays ; Genomics

Abstract

The original observation of altered DNA methylation in cancer was widespread hypomethylation affecting as many as 1/3 of single copy genes and arising at the earliest stages. Later studies identified CpG island hypermethylation as well. More recently large heterochromatin regions termed LOCKs were found to become euchromatic in cancer lines. Recent whole genome bisulfite sequencing studies of human colorectal cancer showed that hypomethylation affects large genomic regions corresponding to chromatin regions (LOCKs) and nuclear organization (LADs), accounting for >95% of the DNA methylation change in cancer. Here we examined 30+ cancer normal pairs of breast, colon, lung, thyroid, [] using the 450K Illumina methylation array. We find that the vast majority of the island hypermethylation is contained within the aberrantly methylated blocks blocks, consistent with our model that these regions represent domains of epigenetic instability with both high and low methylation regressing to middle values. The data suggest the methylation dysregulation occurs early and the instability affecting islands is progressive through stages of tumor development.