Rahbari and Cortes Ciriano groups wearing blue for Li Fraumeni Syndrome (LFS) Awareness Day 2022. Image credits: Wellcome Sanger Institute and EMBL-EBI

Categories: Sanger Science18 March 20223 min read

LiFTS: Li Fraumeni over Time Study – tracking changes in LFS

March 20th is Li Fraumeni Syndrome (LFS) Awareness Day. People will be on social media, wearing blue, #WearBlueForLFS, to raise awareness of this little-known cancer syndrome.

People with LFS have typically inherited an inactive TP53 gene, known as the ‘guardian of the genome’. A healthy TP53 gene acts as a tumour suppressor, repairing DNA damage as and when it occurs, and prevents cancers forming. For those with LFS and a mutation in TP53, there is usually a near 100 per cent risk of developing at least one type of cancer during their life time.

Researchers at the Wellcome Sanger Institute and EMBL's European Bioinformatics Institute (EMBL-EBI) have just been awarded £1.4 million from the Medical Research Council to study LFS, with the aim of improving early detection and prevention.

So much about Li Fraumeni Syndrome (LFS) is unknown. We know that most people with LFS have inherited a mutation in the TP53 tumour suppressor gene. But this isn’t always the case. Some people develop the mutation as a baby in the womb, rather than inherit it. And there are others who have the mutation in some cells, but not others, known as mosaic cases. Plus, there are some people who have LFS, and a family history of the disease, but no known genetic cause - they don’t have a TP53 mutation at all.

We know that LFS is associated with high cancer risk. Except, there are people who never get cancer, despite having the condition. In some families, a TP53 mutation seems to cause different cancers in different people. And, we don’t know why an individual’s cancer risk changes over time.

The lack of knowledge prevents us finding treatments to reduce the risks of cancer. It stops us developing better surveillance techniques to catch cancers early. It makes it hard to estimate risks for individual people with LFS. There are so many questions, and the only way to answer them is through more research.

This is where LiFTS (Li Fraumeni over Time Study) comes in. It’s a fantastic new project, co-led by Dr Raheleh Rahbari at the Sanger Institute and Dr Isidro Cortés-Ciriano at EMBL-EBI. The study has been developed thanks to the support of the Medical Research Council and the George Pantziarka TP53 Trust. Our aim is to understand the biology of living with LFS. Specifically, we want to understand why the frequency of cancer, and the age of cancer onset, varies depending on where the cancer arises. We are also investigating why some mutations in TP53 are associated with a higher risk of developing cancer than others. To do this, we will use sophisticated methods to analyse the alterations in the DNA of cells, as these occur during life, and we will take samples from volunteers over a number of years and track the changes. Our ultimate goals are to improve our understanding of cancer development and to improve the lives of LFS patients.

It’s a great pleasure to announce this new project on LFS Awareness Day 2022.

The study is now open to participants. To find out more, please contact us.

Dr Raheleh Rahbari    rr11@sanger.ac.uk

Dr Isidro Cortes-Ciriano   icortes@ebi.ac.uk

Dr Pan Pantziarka  anticancer.org.uk@gmail.com

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