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- W2334462362 abstract "Alterations in DNA methylation in human cancer were identified 30 years ago but a comprehensive view has emerged with the advent of whole genome bisulfite sequencing. While cancer can be viewed as over 200 distinct diseases that are organ-specific in their pathology, and mutation-specific in their molecular mechanism, recent discoveries in cancer epigenetics suggest a different but complementary view. Epigenetically, cancer may approach a single disorder with certain common features underlying the major reasons for cancer morbidity and mortality. Specifically, several common solid tumor types show increased epigenetic instability in DNA methylation at specific loci but involving the same loci in many different tumor types, and these loci appear to be critical for unregulated cell growth and tissue invasion and metastasis, and they involve the boundaries between CpG islands and shores, as well as large hypomethylated genomic blocks. These blocks correspond to large organized chromatin lysine (K) -modified domains (LOCKs) that are normally modulated during cellular reprogramming in development and epithelial-mesenchymal transition. We suggest a unifying model for the epigenetic basis of cancer in which increased instability in gene expression is mediated by loss in cancer of nuclear structures that control variance during normal development, such as LOCKs and CpG island boundaries. By this view, stochastic noise is a necessary part of cell fate determination leading to Waddingtonian canalization, and cancer is a disease, at least epigenetically, in which these canals are shallower, with increasing noise and the probability of cell type transitions that should not appear in differentiated tissues. At the same time, this increased noise increases the fitness of cancer cells and their resistance to any given therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY21-02. doi:1538-7445.AM2012-SY21-02" @default.
- W2334462362 created "2016-06-24" @default.
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- W2334462362 date "2012-04-15" @default.
- W2334462362 modified "2023-09-27" @default.
- W2334462362 title "Abstract SY21-02: DNA methylation and epigenetic instability in human cancer" @default.
- W2334462362 doi "https://doi.org/10.1158/1538-7445.am2012-sy21-02" @default.
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