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Genome Medicine

, 6:61

1. Genomics and epigenomics of disease1. Genomics and epigenomics of disease


BackgroundOne of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs large organized chromatin lysine-modifications and LADs lamin-associated domains.

MethodsHere we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform.

ResultsWe find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks.

ConclusionThus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors.

Electronic supplementary materialThe online version of this article doi:10.1186-s13073-014-0061-y contains supplementary material, which is available to authorized users.

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Autor: Winston Timp - Hector Corrada Bravo - Oliver G McDonald - Michael Goggins - Chris Umbricht - Martha Zeiger - Andrew P Fe


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