Cancer epigenetics

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Normal-cancer-epigenome

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Epigenetic alterations in tumour progression

DNA methylation

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DNA damage, repair, alteration of repair in cancer

Decitabine

Cancer epigenetics is the study of epigenetic modifications to the DNA 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 the context of cancer, epigenetics refers to the heritable changes in gene expression that occur without alteration in the DNA sequence itself.

Overview

Cancer epigenetics involves the study of changes in the regulation of gene activity and expression that are not dependent on gene sequences. These changes can include DNA methylation, histone modification, and alterations in the structure of chromatin that collectively influence chromosomal architecture and gene expression. These epigenetic modifications can lead to the silencing of tumor suppressor genes or the activation of oncogenes without altering the DNA sequence, contributing to the development and progression of cancer.

DNA Methylation

DNA methylation is a critical epigenetic modification involving the addition of a methyl group to the DNA molecule, usually at cytosine bases in the context of CpG dinucleotides. In cancer, abnormal DNA methylation patterns can lead to the silencing of tumor suppressor genes, promoting uncontrolled cell growth and division. DNA methylation is one of the most extensively studied epigenetic mechanisms in cancer.

Histone Modification

Histone modifications include the addition or removal of chemical groups such as methyl, acetyl, phosphate, and ubiquitin to the histone proteins around which DNA is wound. These modifications can alter the accessibility of the DNA to transcription factors and other proteins, thereby regulating gene expression. In cancer, aberrant histone modifications can result in the inappropriate activation or silencing of genes involved in cell cycle regulation, apoptosis, and DNA repair.

Chromatin Remodeling

Chromatin remodeling refers to the dynamic modification of chromatin architecture to regulate access to genetic information in the DNA, influencing gene expression. Changes in chromatin structure can be mediated by ATP-dependent chromatin remodeling complexes. In cancer, alterations in chromatin remodeling can disrupt the normal regulation of gene expression, contributing to cancer progression.

MicroRNAs and Non-coding RNAs

MicroRNAs (miRNAs) and other non-coding RNAs play a significant role in cancer epigenetics by regulating gene expression at the post-transcriptional level. miRNAs can bind to complementary sequences on messenger RNA molecules, leading to their degradation or the inhibition of their translation. Dysregulation of miRNAs has been implicated in various cancers, affecting cell proliferation, apoptosis, and metastasis.

Clinical Implications

Understanding the epigenetic mechanisms underlying cancer has significant clinical implications. Epigenetic changes are reversible, making them attractive targets for cancer therapy. Drugs targeting DNA methylation and histone deacetylation have been approved for the treatment of certain cancers. Furthermore, epigenetic markers can serve as biomarkers for cancer diagnosis, prognosis, and monitoring response to treatment.

Research and Future Directions

Research in cancer epigenetics is rapidly advancing, with ongoing studies aimed at understanding the complex interplay between genetic and epigenetic changes in cancer. Future directions include the development of more targeted epigenetic therapies, the identification of novel epigenetic biomarkers for cancer detection and prognosis, and the exploration of the role of the epigenome in resistance to cancer therapies.