TY  - JOUR
A1  - Hansen, Kasper D.
A1  - Sabunciyan, Sarven
A1  - Langmead, Ben
A1  - Nagy, Noemi
A1  - Curley, Rebecca
A1  - Klein, Georg
A1  - Klein, Eva
A1  - Salamon, Daniel
A1  - Feinberg, Andrew P.
T1  - Large-scale hypomethylated blocks associated with Epstein-Barr virus–induced B-cell immortalization
Y1  - 2014/02/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 177 
EP  - 184 
DO  - 10.1101/gr.157743.113 
VL  - 24 
IS  - 2 
UR  - http://genome.cshlp.org/content/24/2/177.abstract 
N2  - Altered DNA methylation occurs ubiquitously in human cancer from the earliest measurable stages. A cogent approach to understanding the mechanism and timing of altered DNA methylation is to analyze it in the context of carcinogenesis by a defined agent. Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma, but also used commonly in the laboratory to immortalize human B-cells in culture. Here we have performed whole-genome bisulfite sequencing of normal B-cells, activated B-cells, and EBV-immortalized B-cells from the same three individuals, in order to identify the impact of transformation on the methylome. Surprisingly, large-scale hypomethylated blocks comprising two-thirds of the genome were induced by EBV immortalization but not by B-cell activation per se. These regions largely corresponded to hypomethylated blocks that we have observed in human cancer, and they were associated with gene-expression hypervariability, similar to human cancer, and consistent with a model of epigenomic change promoting tumor cell heterogeneity. We also describe small-scale changes in DNA methylation near CpG islands. These results suggest that methylation disruption is an early and critical step in malignant transformation. 
ER  -