Epigenetic reveals early breast cancer development

Changing the epigenetic code of a single gene is enough to cause a healthy breast cell to begin a chain reaction and become abnormal, Epigenetic changes are a hallmark of cancer, but up until now, it has not been known whether these changes on their own are sufficient to push healthy cells down the cancer path.

 Using a CRISPR-dCas9 epigenetic editing tool, the researchers methylated different genes in healthy breast cells and found that those changes were sufficient to cause the cells to undergo hyperproliferation - abnormally rapid cell division which is an early stage of tumour initiation.

The epigenetic changes are inherited as long as the cell divides, and that the team's manipulations permanently and negatively affected the biology of a normal breast cell from a healthy individual. Epigenetic editing could also be used to design novel therapies by initiating permanent changes to cell biology.

This may be a more viable or alternative way forward for gene editing as any potential mistakes would be less damaging than directly editing the DNA sequence, and epigenetic editing would be more easily reversible if needed. Epigenetic fluctuations happen all the time in human cells. During ageing, human epigenome is progressively distorted.
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Chemotherapy may have effects on intergenerational fertility

Chemotherapy treatment can damage the fertility of women and their children. The treatment can reduce the levels of fertility and chance of having children. Women and men are encouraged to freeze their eggs or sperm before treatment.

But when chemotherapy patients have children naturally, it was usually assumed that their ability to reproduce was unaffected. Children born to women who have had chemotherapy have 72 per cent fewer children of their own than members of the general population.

The effect seems to mainly affect women. Children of men who had chemotherapy treatment may have a similar number of children compared to members of the general population of the same age. Daughters of women who had chemotherapy had 71 per cent fewer children than the general population. Sons of female chemotherapy patients had 87 per cent fewer children.

 This may be caused by epigenetics or changes which can be compared to switches that turn on or off certain genes in the DNA passed on to a person’s offspring. Recent studies have found that, smoking causes epigenetic changes in DNA. Chemotherapy given to women may have intergenerational effects on fertility.
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Maternal diet may increase the risk of disease in fetus

Research has shown that a mother's diet during pregnancy, particularly one that is high-fat, may program her baby for future risk of certain diseases such as diabetes. Changing the baby's diet to a low-fat diet can change the effects of maternal diet. Early-life nutrition affects later generations and offspring health. Epigenetics does not involve changes to the DNA sequence, but are changes that modify gene expression. A person's epigenome is inherited, but it is also reversible based on what you eat, whether you exercise, and even where you live.

The researchers examined rats that were exposed to a high-fat diet during gestation and lactation. At weaning, some of the rats stayed on a high-fat diet and some were put on a low-fat diet. The researchers then did whole-genome sequencing of the rats, focusing on differences between gene expression in the livers of the two sets of rats. In particular, they wanted to see if DNA methylation in the liver adapted to the new, low-fat diet. DNA methylation is a mechanism cells use to control gene expression at the epigenetic level. It involves the addition of a methyl group to DNA that changes the way genes are transcribed and affects gene expression.

Scans showed remodeled DNA methylation patterns in the low-fat group, which changed gene expression associated with fat metabolism and inflammation in the liver; there was less fat accumulation and inflammation in the liver. This shows that DNA methylation is responsive to dietary changes later in life. While there were physiological changes in the rats on low-fat diets, including lower body weight.

The early-life environment will mark your epigenome in a certain way so that you may develop certain phenotypes or disease states. Our study shows that after that early programming state, after weaning, and after the lactation period, when we introduced a new type of diet it changed the epigenome in a way that actually affects metabolism and potentially will reduce some of the damage caused by an early-life high-fat exposure. Switching to a different diet you can specifically remodel the epigenome in the liver related to certain metabolic pathways.
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