Wellcome Sanger Institute

Li Fraumeni over Time Study (LiFTS)

The LiFTS study explores which changes in the DNA of adults and children with Li Fraumeni Syndrome increase the risk of developing cancer. To do this, we study DNA samples from people with conditions such as Li Fraumeni Syndrome and compare them with the DNA from their parents, siblings and close relatives. We hope that this will lead to a better understanding of which mutations cause disease predisposition and how they are passed down to the next generation.

People with Li Fraumeni Syndrome 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 people with Li Fraumeni Syndrome this change to their TP53 gene usually means that they have a near 100 per cent risk of developing at least one type of cancer during their lifetime.

But there is much that we don’t currently understand about the syndrome and how it affects people over their lifetime – and discovering the answers may help with the development of future diagnostic tests and treatments.

Aspects of Li Fraumeni Syndrome we are looking to explore

The majority of people inherit Li Fraumeni Syndrome from their parents, but this is not true for everyone. For example, some people spontaneously develop a change in their TP53 gene as a baby in the womb. While other people have a mosaic version of the disease; where some of their cells have an inactive version of TP53, while others don’t.

There are some people who have Li Fraumeni Syndrome, and a family history of the disease, who don’t have a change in their TP53 gene at all! The cause of their increased risk of developing cancer is unknown.

In contrast, there are some people who have Li Fraumeni Syndrome but who never develop cancer, despite having an inactive TP53 gene.

In addition, changes in the TP53 gene appear to cause different cancers in different people.

And, finally, we know Li Fraumeni Syndrome causes a person’s risk of developing cancer to change over time, but we don’t have the answers of how or why.

This 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 Li Fraumeni Syndrome.

There are so many questions, and the only way to answer them is through more research.

Who are we?

We are a group of researchers and oncologists aiming to improve early detection and prevention for individuals with Li Fraumeni Syndrome and or other cancer predisposition syndrome. We have just been awarded £1.4 million from the Medical Research Council for this study.

Dr Raheleh Rahbari, Wellcome Sanger Institute

Dr Isidro Cortes-Ciriano, EMBL-European Bioinformatics Institute

Dr Pan Pantziarka, The George Pantziarka TP53 Trust

Dr Mette Jorgensen, Great Ormond Street Hospital for Children

What are the goals of the Li Fraumeni over Time Study (LiFTS)?

The Li Fraumeni over Time Study (LiFTS) 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 Li Fraumeni Syndrome. 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 changes 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 multiple samples from volunteers over several years and track the changes.

Our ultimate goals are to improve our understanding of cancer development and to improve the lives of Li Fraumeni Syndrome patients.

What does the study involve?

We would like to collect a range of samples from volunteers every six months to one year over 3-4 years. Samples are including blood, cheek, saliva, semen (male participants), urine. In addition, where volunteers have had a procedure where material has been collected and is available – for example skin biopsies, gastric and colon biopsies, and tumour samples from diagnostic labs – we would like to study these as well.

Volunteers are welcome to contribute some or all of these types of samples.

We will use the samples we collect to measure the number of changes that accumulate in people’s DNA across a wide range of tissues over time.

How will volunteers benefit from the study?

It is unlikely that our study will directly benefit the people who volunteer to take part in the study. However, we hope that the results of our study will provide insights that could help future generations of children born with a disease pre-disposition syndrome such as Li Fraumeni Syndrome.

In addition, we may also find genetic markers that might help clinicians to detect cancer development earlier and, potentially, help with cancer prevention.

How do volunteers register to take part in the study?

Please contact us by sending email to: lifts@tp53.org.uk.

We will then send you a patient information sheet and consent form to send back to us, along with more information on how to take a part in the study.

Sanger people

External Contributors

Photo of Dr Isidro Cortes Ciriano

Dr Isidro Cortes Ciriano

Group Leader, EMBL-EBI

Photo of Dr Mette Jorgensen

Dr Mette Jorgensen

Consultant in Paediatric Oncology, Great Ormond Street Hospital

Photo of Dr Pan Pantziarka

Dr Pan Pantziarka

The George Pantziarka TP53 Trust

External partners and funders