By Pan Pantziarka, Mette Jorgensen (Great Ormond Street Hospital) and Raheleh Rahbari (Sanger Institure)

There are so many things that we still don’t know about Li Fraumeni Syndrome and other cancer predisposition syndromes. People with LFS have what is called a germline mutation in TP53 – that is they are born with the mutation in all their cells (or a significant subset of cells for people with ‘mosaic’ TP53 mutations). For most people with LFS this is something they inherited from one of their parents – but there are also many who are ‘de novo’, that is their parents don’t have a germline mutation that has been passed down to them. But it’s theoretically possible that one or other of the parents may have had a mutation in a germ cell (sperm or egg) and that this mutated cell was fertilised and developed into a child with LFS. Could this be how so many ‘de novo’ cases develop? We don’t know. But we’d certainly like to find out – and now have a chance with a new project being run by Great Ormond Street Hospital and the Sanger Institute, both world-class institutions based in the UK.

For this study we want to collect sperm and blood samples from men who have LFS themselves or who have children with LFS. This includes men with LFS regardless of whether they have children or not, and men who have children with LFS even if they themselves don’t have it (either because it has been passed down from the mother or because the child is ‘de novo’). From women we want to collect blood samples only – collecting eggs is trickier than collecting sperm!

We want this study to be as wide-ranging as possible – so it will include people with LFS-like syndrome (no identified TP53 mutation), TP53 mutations which have been defined as ‘variants of unknown significance’ (VUS) and mutations in associated genes (CHEK2 for example). It will include people who are ‘mosaic’ too.

Male participants in the study will be asked to donate a sperm sample and to have blood collected, as well as answering questions on their family history, TP53 status etc. For women, it’s a blood sample as well as the data collection.

There is so much we can learn from this study – it can open new doors to our understanding of LFS (and other cancer syndromes) and also help to answer some of those long-standing ‘why?’ questions regarding ‘de novo’ mutations. This is a great opportunity to contribute to a cutting edge science project – so please take the opportunity if you think you are eligible. And for those women with LFS who are reading this – you can contribute by passing this on to the men in your lives!

If you are interested in taking part please send an email to: