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has been cited by the following article:

• TITLE: Methylation Abnormalities in Mammary Carcinoma: The Methylation Suicide Hypothesis

  AUTHORS: Anne H. O’Donnell, John R. Edwards, Robert A. Rollins, Nathan D. Vander Kraats, Tao Su, Hanina H. Hibshoosh, Timothy H. Bestor

  KEYWORDS: DNA Methylation, Mammary Carcinoma

  JOURNAL NAME: Journal of Cancer Therapy, Vol.5 No.14, December 3, 2014

  ABSTRACT: Promoter silencing by ectopicde novomethylation of tumor suppressor genes has been proposed as comparable or equivalent to inactivating mutations as a factor in carcinogenesis. However, this hypotheses had not previously been tested by high resolution,high-coverage whole-genome methylation profiling in primary carcinomas. We have determined the genomic methylation status of a series of primary mammary carcinomas and matched control tissues by examination of more than 2.7 billion CpG dinucleotides. Most of the tumors showed variable losses of DNA methylationfrom all sequence compartments, but increases in promoter methylation were infrequent, very small in extent, and were observed largely at CpG-poor promoters. De novo methylation at the promotersof proto-oncogenes and tumor suppressor genes occurred at approximately the same frequency. The findings indicate that tumor suppressor silencing byde novomethylation is much less common than currently believed. We put forward a hypothesis under which the demethylation commonly observed in carcinomas is a manifestation of a defensive system that kills incipient cancer cells.