Abstract
CpG island hypermethylation is a common mechanism for gene silencing of tumor suppressor genes. A specific profile of gene hypermethylation occurs according to the tumor type and CpG island methylation of particular genes have been used for translational purposes. Genes inhibiting cell invasion and dissemination also undergo CpG island hypermethylation-associated inactivation. These metastasis suppressor genes can also become transcriptionally inactive by other epigenetic mechanism such as an aberrant histone code and a compact conformation of chromatin in a highly dynamic manner. The best characterized example is the E-cadherin gene, but the tumor/metastasis suppressor genes with CpG island hypermethylation in cancer include other members of the cadherin family (H-cadherin, R-cadherin, FAT), heparan sulfate genes (EXT1, GPC3, 3-OST-2), tissue inhibitors of proteinases (TIMP2, TIMP3, TFPI-2), axon guidance molecules (SEMA3B, SLIT-1, SLIT-2, SLIT-3), thrombospondins (THBS1, THBS2) and laminin genes (LAMA3, LAMB3, LAMC2). Preliminary data suggest that DNA demethylating drugs, reactivating these dormant methylated metastasis genes, have an effect against the development of metastasis.
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Esteller, M. (2005). How CpG Island Hypermethylation Leads to Cancer Dissemination: The Sounds of Silence for Tumor and Metastasis Suppressor Genes. In: Esteller, M. (eds) DNA Methylation, Epigenetics and Metastasis. Cancer Metastasis — Biology and Treatment, vol 7. Springer, Dordrecht. https://doi.org/10.1007/1-4020-3642-6_1
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DOI: https://doi.org/10.1007/1-4020-3642-6_1
Publisher Name: Springer, Dordrecht
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