TY  - JOUR
A1  - Easwaran, Hariharan
A1  - Johnstone, Sarah E.
A1  - Van Neste, Leander
A1  - Ohm, Joyce
A1  - Mosbruger, Tim
A1  - Wang, Qiuju
A1  - Aryee, Martin J.
A1  - Joyce, Patrick
A1  - Ahuja, Nita
A1  - Weisenberger, Dan
A1  - Collisson, Eric
A1  - Zhu, Jingchun
A1  - Yegnasubramanian, Srinivasan
A1  - Matsui, William
A1  - Baylin, Stephen B.
T1  - A DNA hypermethylation module for the stem/progenitor cell signature of cancer
Y1  - 2012/05/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 837 
EP  - 849 
DO  - 10.1101/gr.131169.111 
VL  - 22 
IS  - 5 
UR  - http://genome.cshlp.org/content/22/5/837.abstract 
N2  - Many DNA-hypermethylated cancer genes are occupied by the Polycomb (PcG) repressor complex in embryonic stem cells (ESCs). Their prevalence in the full spectrum of cancers, the exact context of chromatin involved, and their status in adult cell renewal systems are unknown. Using a genome-wide analysis, we demonstrate that ∼75% of hypermethylated genes are marked by PcG in the context of bivalent chromatin in both ESCs and adult stem/progenitor cells. A large number of these genes are key developmental regulators, and a subset, which we call the “DNA hypermethylation module,” comprises a portion of the PcG target genes that are down-regulated in cancer. Genes with bivalent chromatin have a low, poised gene transcription state that has been shown to maintain stemness and self-renewal in normal stem cells. However, when DNA-hypermethylated in tumors, we find that these genes are further repressed. We also show that the methylation status of these genes can cluster important subtypes of colon and breast cancers. By evaluating the subsets of genes that are methylated in different cancers with consideration of their chromatin status in ESCs, we provide evidence that DNA hypermethylation preferentially targets the subset of PcG genes that are developmental regulators, and this may contribute to the stem-like state of cancer. Additionally, the capacity for global methylation profiling to cluster tumors by phenotype may have important implications for further refining tumor behavior patterns that may ultimately aid therapeutic interventions. 
ER  -