Epigenetics and Cancer

What is Epigentics?

Epigenetics is the study of cellular and physiological phenotypic (observable) trait variations that result from external or environmental factors that switch genes on and off and affect how cells express genes. These alterations may or may not be heritable. Unlike genetics based on changes to the DNA sequence (the genotype), the changes in gene expression or cellular phenotype of epigenetics have other causes. The term also refers to the changes themselves: functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence.

What is Cancer Epigentics?

Cancer epigenetics is the study of epigenetic modifications to the genome of cancer cells that do not involve a change in the nucleotide sequence. Epigenetic alterations are as important as genetic mutations in a cell's transformation to cancer, and their manipulation holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. Several medications which have epigenetic impact are now used in several of these diseases.

Epigenetic changes in mouse produces Cancer --A mouse model has been created providing the first in vivo evidence that epigenetic alterations alone can cause cancer. Epigenetic alterations don't change the DNA sequence but how it is 'read.' In particular, DNA methylation, the addition of a methyl group (or molecule), is an epigenetic switch that can stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can. Until now, direct evidence that DNA methylation drives cancer formation was lacking... The engineered p16Ink4a promoter hypermethylation led to transcriptional suppression in somatic tissues during aging and increased the incidence of spontaneous cancers in these mice. See Reference 1 and 2.

Micro RNA's and Epignetics

MicroRNAs (miRNAs) are small RNA molecules, ~22 nucleotides long that can negatively control their target gene expression posttranscriptionally. There are currently more than 460 human miRNAs known, and the total number is predicted to be much larger. The expression of miRNAs has recently been linked to cancer development, and miRNA profiles can be used to classify human cancers. (See Reference 3- Review) miRNAs are encoded in our genome and are generally transcribed by RNA polymerase II. "...miRNAs have recently been shown to be definitely linked to cancer, and they can act as either oncogenes or tumor-suppressor genes in carcinogenesis. For example, miR-15a and miR-16-1 can target the anti-apoptotic BCL2, and they are often down-regulated in chronic lymphocytic leukemia miR-21 is found to be antiapoptotic, and it is up-regulated in glioblastomas and breast cancers . Lu et al. showed that the expression profiles of miRNAs are able to classify human cancers. (See Reference 3 - Review article.)


Readings and References

1-Epigenetic Changes Can Cause Cancer

2-Targeted p16Ink4a epimutation causes tumorigenesis and reduces survival in mice

3-Epigenetics and MicroRNAs

4-Big Question: Can your environment change your DNA?