Genetic testing for possible missed cases of Lynch syndrome

Lead researcher: Dr James Whitworth 

Location: University of Cambridge 

Grant award: £33,148 

Dr Whitworth is studying special cases of Lynch syndrome that would be missed by standard genetic testing. 

The challenge 

Lynch syndrome is a genetic condition, caused by certain gene changes (mutations), that increases the risk of some types of cancer, particularly bowel cancer. Around eight in 10 people with Lynch syndrome will develop bowel cancer during their lifetime. 

It’s important that people with Lynch syndrome are identified. It determines the best type of therapy for their cancer, allows them to be properly monitored for any future cancers and means their relatives can also be tested. Everyone in the UK diagnosed with bowel cancer should be tested for Lynch syndrome — currently this is usually done via a blood test.

Sometimes, rather than a genetic condition affecting someone’s entire body, they have a form called mosaicism. Someone with a mosaic condition only has the genetic mutations in some parts of their body, while other parts have the correct version of the gene.

If someone had a mosaic form of Lynch syndrome, they might have the syndrome in their bowel and be at higher risk of cancer, but not show the mutation in their blood. They might not be diagnosed with Lynch syndrome and so wouldn't get the right treatment.

At the moment, we don’t know how common mosaic Lynch syndrome might be, or how many patients might be being missed because of it.

The science behind the project

Dr Whitworth’s team will study patients who developed multiple Lynch syndrome-related tumours and were suspected of having Lynch syndrome, but whose blood test came back negative. 

The researchers will analyse stored samples of the tumours to look for the genetic changes that cause Lynch syndrome, to check if they’re present in the tumour even though they weren’t found in the blood. 

If they do find the mutations, they’ll also test other samples from the patients, such as saliva and urine, to see if the mutations can be found anywhere else.

What difference will this project make?

We need to make sure everyone with Lynch syndrome has been diagnosed, so that their condition can be properly managed. This project will help to understand if mosaicism has been under-considered in Lynch syndrome. 

If the study shows that mosaic Lynch syndrome is more common than had been thought, it could lead to changes in how Lynch syndrome is diagnosed in the clinic. For example, if a patient has a negative blood test but develops more than one Lynch-related cancer, further genetic testing could be done on other samples from that person, or using different techniques.

• For more information see our announcement of the grant
• Find out more about Lynch syndrome 

• Donate and help make our research possible 

“Lynch syndrome is the most common inherited cause of bowel cancer, and spotting it early means we can prevent cancer or catch it sooner. We think some cases might be missed because the genetic change that causes Lynch syndrome isn’t always present in every part of the body (referred to as mosaicism), so a standard blood test might not pick it up. 

Through this project, we’ll explore how often this happens and whether current testing methods need to change. We’ll be studying samples from people who’ve developed more than one primary tumour - an area I’ve been really interested in for some time. I hope our findings will help improve diagnosis for people with Lynch syndrome and also support me as I take the next step towards running my own independent research programme.” - Dr James Whitworth