Epigenetics At A Glance
Cancer
Timeline of Major Advances in Human Cancer Epigenetics
Genetic Markers Related to Prostate, Breast and Ovarian Cancer Discovered
Scientists at the University of Cambridge and the Institute of Cancer Research in London conducted an experiment that examined the DNA of 200,000 people, half of them with cancer and the other half without. With this, they discovered 80 genetic markers that could increase a person's risk of developing prostate, breast or ovarian cancer. These discoveries represent 40% of total genetic risk factors for these three types of cancers (31). It is believed that within five years, this discovery will lead medical experts to develop a simple saliva testing for these risk factors (32).
In the past decade, there here has been great interest in the concept of cancer being a disease of epigenetic abnormalities. Overall changes in levels of histone modifications important to activation and repression of gene transcription have been reported in tumors and the blood of patients with cancer (29). Decreases and increases in DNA methylation have also been recognized in cancer DNA over the past 20 years (29). It is believed that misregulation in DNA methylation, histone modification or nucleosome remodeling can lead to cancer.
Breakthroughs in Cancer and Epigenetics
Epigenetic Therapies Taking on Lung Cancer
Stephen Baylin and his team of researchers at Johns Hopkins School of Medicine in Baltimore have discovered that a combination of a histone-deacetylase inhibitor and azacitidine slowed down tumour growth in some people with advanced lung cancer. This result was a big achievement because it was the first time epigenetic drugs had been deployed successfully against a solid tumour since solid tumours are harder to treat because the drug has to penetrate them. Also, some of the participants in Dr Baylin's study who did not show much response to the trial itself then went on to show an unexpectedly good reaction to the routine chemotherapeutic drugs which were given to them next. Although it this research is still unsure, Dr Baylin believes that his epigenetic drugs altered the tumour cells in some lasting way that made them more susceptible to standard chemotherapy (33).
Unlike other forms of gene regulation, epigenetic changes are passed on during cell division to daughter and granddaughter cells until they are actively erased which could be what make Dr. Baylin's discoveries possible. Once erased, they do not return, therefore epigenetic therapies can keep a cancer from growing without having to kill all its cells (33).
The Effect the Amount of Methyl Has on Cancer Cells
Cancer cells that have more methyl than healthy cells do have less active DNA. The genes that repair DNA, regulate cell growth, and start the programmed death of a cell are turned off in cancer cells.
Essential in assuring that the packaging of genomes in chromatin remain flexible and adaptable to regulatory needs, nucleosome remodeling enzymes use the energy of ATP to alter histone DNA interactions. It is involved in the assembly of stable chromatin structures and even contributes structural information to these chromatin structures. Chromatin structures are one of the main components in deciding which genes are expressed and which are suppressed and if the wrong genes are turned off, a normal cell could be converted into a cancer cell. (20)
Nucleosome Remodeling
Cancer cells have less methyl than healthy cells do, which leads to more active DNA. Having less methyl need for proper, healthy functioning can lead to a loss of imprinting, the active DNA being duplicated, removed, or deleted and affect the activation of genes that promote cell growth.
Dr. Stephen Baylin of John Hopkins School of Medicine