Determining the Risk of Breast Cancer Using our Genetic Material

My name is Elke and I am a researcher at the University of Manchester. My work focuses on breast cancer: I am interested to discover the role our genetic material has in the development of breast cancer, which is the most common form of cancer in women. Our aim is to predict the likelihood of developing breast cancer for each individual. My work mostly focuses on families with many women affected with breast cancer, for reasons that aren’t yet understood.

Advancing knowledge on genetic factors involved in breast cancer development is one of the key factors for managing breast cancer risk: women with genetic changes likely to cause cancer can get more intensive screening and can take other preventative measures, such as breast removal. As you may know, this is also what Angelina Jolie did, when she found out that she had a fault in the BRCA1 gene. Another advantage of knowing the genetic fault you may have is that if you develop breast cancer, certain treatments may work better if we know which genes are faulty.

We already know of a lot of these genetic changes and their effects. However, there are still many changes for which we don’t know their impact, so one approach is to identify their effects. Recently, a new method, called CRISPR, has been developed. This method makes it easier to make the exact changes in our genetic material researchers like myself are interested in. What this new method really is, is a DNA scissor. The brilliant thing about this scissor is that it can be used to cut specifically where you want it to.

Our cells have ingenious systems to repair breaks (or specific cuts made by using CRISPR) in our DNA. One method our cells use is called non-homologous end joining, whereby both ends of a strand of DNA are pasted back together. This is not very precise however, and some changes to the original DNA template will occur. This can be handy if we want to study what larger and imprecise changes do to the function of that specific region of our DNA. These larger changes are thought to often be the reason genes become faulty and cause disease.

Another method to repair DNA breaks is very precise: homologous recombination. This method uses an exact template of the region where the break occurs and repairs it back to its original state, otherwise known as its base order. We can use homologous recombination to ‘trick’ the system and perform the exact changes we want. In our case, we designed a ‘repair template’ with the variants we wanted to examine for their effect on the function of a breast cancer-associated gene.

In the lab, we add our specific DNA ‘scissors’ and our specific repair template into cells. Once we have confirmed that the variant/fault we are interested in is present in the DNA of the cells, we can test the function of the gene and in that way determine if that particular change has no impact or is actually responsible for making the gene faulty. By doing this, we get to know more about variants and can inform families about what the effect of carrying this defect is. This can then inform their treatment plans.

Other uses of CRISPR

There are several other ways CRISPR can be used, such as to alter the DNA ‘scissor’ in such a way that it cannot cut anymore. It will still recognise a specific piece of DNA but will not damage it. However by occupying that piece of DNA, the scissor can disrupt its function by blocking access to other elements that are required for gene expression. Different DNA ‘scissors’ have different cutting patterns, which can be used in specific experiments. There are also several different types of these CRISPR DNA ‘scissors’ that can recognise genetic material belonging to, for example, viruses. These specific properties have already been used in the development of rapid diagnostic tests in order to determine if someone has been infected with a certain pathogen.