Studying fruit flies to unravel the cause of hereditary cancers

22nd January 2024

A team of Worldwide Cancer Research scientists in France have studied the genetic code of fruit flies to investigate what goes wrong when inherited genes trigger a tumour to grow. The researchers hope that what they have learned in fruit flies could apply to cancer in humans, and in future lead to the development of drugs that can prevent familial or hereditary cancers from starting.

What is a familial or hereditary cancer?

Cancer is a genetic disease. That means that it can develop when there is a problem, or a “mutation”, in one piece of the genetic material that makes up the instructions our cells use to function properly. Some of these mutations happen in our bodies over time, and can be caused by things like sun damage or smoking.

Other genetic mutations can be passed on from parents to children - just as you might have inherited genes that give you your mum’s eye colour or your dad’s hair type, genetic mutations that affect your ability to fight cancer can also be inherited. This is why certain types of cancer run in families, and it can happen when the inherited gene that is affected is a tumour suppressor: one that, when working properly, prevents tumours from growing. Mutations that lose these tumour suppressors can lead to specific types of cancer, for example some breast cancers, or a syndrome known as familial adenomatous polyposis, which puts people at a high risk of developing colorectal and other cancers.

These inherited gene mutations usually exist without any issues in our body, because we inherit two copies of each piece of genetic code: one from each of our biological parents. If only one copy has the mutation, then our body can function normally following the instructions in the healthy copy. When this is the case, we say the gene is heterozygous: hetero is Greek for “different”, because there are two different copies of that piece of genetic code. However, on rare occasions something causes the second copy to mutate too, leaving the code without tumour suppressor instructions and allowing cancer to develop. This is known as loss of heterozygosity.

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What exactly is it that causes these genes to mutate? And is there anything we can do to prevent that from happening?

With support from our Curestarters, researchers Dr Allison Bardin, Lara Al Zouabi and Marine Stefanutti set out to find the answer to this question. Understanding this better could have huge consequences for families with a history of cancer and help us prevent hereditary cancers like retinoblastoma – a rare eye cancer that affects young children.

To investigate these genetic changes, the researchers looked at what happens in fruit fly intestines when cancer starts to develop. Fruit flies are often used for genetic studies as their genetic material is 16 times smaller than the genome of humans or other mammals, which makes it quicker and easier to study. They also have a short lifespan of only a few weeks, which makes studying the ageing process much quicker!

This image shows a fly intestine under the microscope - the pink dots show where a tumour is growing due to loss of heterozygosity.

What did the researchers find?

The team employed a technique called whole genome sequencing, using state-of-the-art technology at the Institut Curie in Paris. This allows the researchers to study each part of the genetic code in detail and identify where changes have occurred. Dr Bardin’s team successfully identified the mechanism that causes loss of heterozygosity and starts cancer – and also discovered that a particular bacterial infection can increase the chances of it happening.

This suggests that it is not only our genes, but also the bacteria that live inside our gut – also known as the microbiome – that can play a role in how cancer develops. Even more importantly, the researchers identified enzymes that can prevent loss of heterozygosity, paving the way for developing future treatments that could prevent cancers from starting. The team’s next steps are to investigate how these changes evolve over time. They also hope that this discovery could be a jumping off point for other scientists to identify drugs that could tackle this process of gene mutation.

What does this breakthrough mean for patients and people concerned by hereditary cancers?

This discovery is a crucial step in understanding how cancer starts, and how we can begin to prevent it in people who have a cancer gene that runs in their family. While inheriting a gene like this doesn’t mean you will definitely get cancer, learning that your genes increase your risk of developing cancer can be very worrying, and as yet we do not have very many preventative treatments for patients at high risk of familial cancers. This research is the first step in changing that, and it’s thanks to the support of our Curestarters that pioneering research breakthroughs like this are possible.

Dr Bardin’s paper has been published, and is available online to read here.

Dr Allison Bardin, Worldwide Cancer Research scientist

We had some really exciting observations that indicated that we had seen something that people hadn’t really noticed before, and we had a difficult time getting funding for this precisely because it was hard for others to believe that we had found something that had been overlooked. This was where Worldwide Cancer Research became really important for us and provided us with support at a critical moment in the project.

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