[1] All mammalian cells descended from a fertilized egg (a zygote) share a common DNA sequence (except for new mutations in some lineages).
The changes include histone modifications, CpG island methylations and chromatin reorganizations which can cause the stable silencing or activation of particular genes.
[4] In colorectal cancers about 600 to 800 genes are transcriptionally silenced, compared to adjacent normal-appearing tissues, by CpG island methylation.
Causes of DNA hypermethylation are: - Mediation of mutated K-ras induced jun protein (Serra RW.
1991) - Other, unspecified reasons for supplying the Met cycle with single-carbon fragments, causing e.g. "methyl trap" phenomenon (Shane B. Stokstad EL.
In cancers, loss of expression of genes occurs about 10 times more frequently by hypermethylation of promoter CpG islands than by mutations.
However, much more frequently, reduced or absent expression of a DNA repair gene in cancer is due to methylation of its promoter.
[16] Twenty-two DNA repair genes with hypermethylated promoters, and reduced or absent expression, were found to occur among 17 types of cancer, as listed in two review articles.
As discussed by Jin and Roberston in their review,[17] silencing of a DNA repair gene by hypermethylation may be a very early step in progression to cancer.
Such silencing is proposed to act similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer.
In an early study, looking at a limited set of transcriptional promoters, Fernandez et al.[32] examined the DNA methylation profiles of 855 primary tumors.
[33] Individual miRNAs can each target, and repress transcription of, on average, roughly 200 messenger RNAs of protein coding genes.
Ruben Agrelo,* Wen-Hsing Cheng,† Fernando Setien,* Santiago Ropero,* Jesus Espada,* Mario F. Fraga,* Michel Herranz,* Maria F. Paz,* Montserrat Sanchez-Cespedes,* Maria Jesus Artiga,* David Guerrero,‡ Antoni Castells,§ Cayetano von Kobbe,* Vilhelm A. Bohr,† and Manel Esteller*¶Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer.Proc Natl Acad Sci U S A.