The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores Export

@article{citeulike:3975458, abstract = {For the past 25 years, it has been known that alterations in DNA methylation (DNAm) occur in cancer, including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes. However, most studies of cancer methylation have assumed that functionally important DNAm will occur in promoters, and that most DNAm changes in cancer occur in CpG islands. Here we show that most methylation alterations in colon cancer occur not in promoters, and also not in CpG islands, but in sequences up to 2 kb distant, which we term 'CpG island shores'. CpG island shore methylation was strongly related to gene expression, and it was highly conserved in mouse, discriminating tissue types regardless of species of origin. There was a notable overlap (45–65\%) of the locations of colon cancer–related methylation changes with those that distinguished normal tissues, with hypermethylation enriched closer to the associated CpG islands, and hypomethylation enriched further from the associated CpG island and resembling that of noncolon normal tissues. Thus, methylation changes in cancer are at sites that vary normally in tissue differentiation, consistent with the epigenetic progenitor model of cancer, which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer.}, author = {Irizarry, Rafael A. and Ladd-Acosta, Christine and Wen, Bo and Wu, Zhijin and Montano, Carolina and Onyango, Patrick and Cui, Hengmi and Gabo, Kevin and Rongione, Michael and Webster, Maree and Ji, Hong and Potash, James B. and Sabunciyan, Sarven and Feinberg, Andrew P.}, citeulike-article-id = {3975458}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ng.298}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ng.298}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19151715}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19151715}, day = {18}, doi = {10.1038/ng.298}, issn = {1061-4036}, journal = {Nature Genetics}, keywords = {array, cancer, charm, colon, cpg, dna, island, methylation}, month = {January}, number = {2}, pages = {178--186}, posted-at = {2009-08-06 20:10:10}, priority = {0}, publisher = {Nature Publishing Group}, title = {The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores}, url = {http://dx.doi.org/10.1038/ng.298}, volume = {41}, year = {2009} }

TY - JOUR ID - citeulike:3975458 L3 - citeulike-article-id:3975458 N2 - For the past 25 years, it has been known that alterations in DNA methylation (DNAm) occur in cancer, including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes. However, most studies of cancer methylation have assumed that functionally important DNAm will occur in promoters, and that most DNAm changes in cancer occur in CpG islands. Here we show that most methylation alterations in colon cancer occur not in promoters, and also not in CpG islands, but in sequences up to 2 kb distant, which we term 'CpG island shores'. CpG island shore methylation was strongly related to gene expression, and it was highly conserved in mouse, discriminating tissue types regardless of species of origin. There was a notable overlap (45–65%) of the locations of colon cancer–related methylation changes with those that distinguished normal tissues, with hypermethylation enriched closer to the associated CpG islands, and hypomethylation enriched further from the associated CpG island and resembling that of noncolon normal tissues. Thus, methylation changes in cancer are at sites that vary normally in tissue differentiation, consistent with the epigenetic progenitor model of cancer, which proposes that epigenetic alterations affecting tissue-specific differentiation are the predominant mechanism by which epigenetic changes cause cancer. IS - 2 JF - Nature Genetics SN - 1061-4036 EP - 186 TI - The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores PB - Nature Publishing Group VL - 41 SP - 178 KW - array KW - cancer KW - charm KW - colon KW - cpg KW - dna KW - island KW - methylation AU - Irizarry, Rafael AU - Ladd-Acosta, Christine AU - Wen, Bo AU - Wu, Zhijin AU - Montano, Carolina AU - Onyango, Patrick AU - Cui, Hengmi AU - Gabo, Kevin AU - Rongione, Michael AU - Webster, Maree AU - Ji, Hong AU - Potash, James AU - Sabunciyan, Sarven AU - Feinberg, Andrew PY - 2009/01/18/ UR - http://dx.doi.org/10.1038/ng.298 ER -