Whole genome sequencing can improve clinical care of childhood cancer

Wellcome Trust Sanger InstituteJul 2 2024

Whole genome sequencing has improved clinical care of some children with cancer in England by informing individual patient care.

New research from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Trust, Great Ormond Street Hospital, and the University of Cambridge, supports the efforts to provide genome sequencing to all children with cancer and shows how it can improve the management of care in real-time, providing more benefits than all current tests combined.

The study, published today (2 July) in Nature Medicine, is the first time that the impact of using whole genome sequencing in current NHS practice has been assessed.

The team analyzed the use of routine genome sequencing, through the NHS Genomic Medicine Service, in two children's cancer centers for solid cancer and leukemia in England. The researchers found that cancer sequencing gave new insights that improved the immediate clinical care of seven per cent of children, while also providing all the benefits of current standard tests.

Furthermore, in 29 per cent of cases, genome sequencing provided additional information that helped clinicians better understand the tumors of individual children and informed future management. For example, uncovering unexpected mutations that increase future cancer risk leading to preventative measures being taken, such as regular screening.

Overall, whole genome sequencing provides additional, relevant data, about childhood cancer that is useful for informing practice. The results also show that it can reduce the number of tests required, and therefore, researchers suggest it should be provided to all children impacted by cancer.

Whole genome sequencing (WGS) is a single test that provides a complete readout of the entire genetic code of the tumor and identifies every single cancer-causing mutation. Comparatively, traditional standard-of-care tests only look at tiny regions of the cancer genome, and therefore many more tests are often required per child.

Whole genome sequencing provides the gold standard, most comprehensive and cutting edge view of cancer. What was once a research tool that the Sanger Institute started exploring over a decade ago, has now become a clinical test that I can offer to my patients. This is a powerful example of the genomic data revolution of healthcare that enables us to provide better, individualized care for children with cancer."

Professor Sam Behjati, senior author from the Wellcome Sanger Institute, Cambridge University Hospitals, and the University of Cambridge

NHS England is one of the few health services in the world that has a national initiative, through the Genomic Medicine Service, offering universal genome sequencing to every child with suspected cancer. However, due to multiple barriers and a lack of evidence from real-time practice supporting its use, whole cancer genome sequencing is not yet widespread practice.

The latest study, from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Trust, Great Ormond Street Hospital, and the University of Cambridge, looked at 281 children with suspected cancer across two English units where this gold-standard test is provided regularly.

The team analysed the clinical and diagnostic information across these units and assessed how genome sequencing affected the care of children with cancer.

They found that WGS changed the clinical management in seven per cent of cases, improving care for 20 children, by providing information that is not possible to acquire from standard of care tests.

Additionally, WGS faithfully reproduced every one of the 738 standard of care tests utilised in these 281 cases, suggesting that a single WGS test could replace the multiple tests that the NHS currently uses if this is shown to be economically viable.

WGS provides a detailed insight into rare cancers, for example, by revealing novel variants of cancer. The widespread use of genome sequencing will enable clinicians to access these insights for individual patients while simultaneously building a powerful shared genomic resource for research into new treatment targets, possible prevention strategies, and the origins of cancer.

Dr Jack Bartram, senior author from Great Ormond Street Hospital NHS Foundation Trust and the North Thames Genomic Medicine Service, said: "Childhood cancer treatment is mostly guided by genetic features of the tumour, and therefore an in-depth genetic understanding of cancer is crucial in guiding our practice. Our research shows that whole genome sequencing delivers tangible benefits above existing tests, providing better care for our patients. We hope this research really highlights why whole genome sequencing should be delivered as part of routine clinical care to all children with suspected cancer."

Eddie's story

When he was six-years old, Eddie began to have regular low-grade fevers that seemed to affect him a lot. Even though early tests came back normal, the fevers became more frequent and his Mum, Harri, noticed that on one or two occasions he seemed out of breath while doing small things like reading a book. A chest x-ray revealed a huge mass on Eddie's chest, and he was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL). Eddie was immediately transferred to Great Ormond Street Hospital (GOSH) to begin treatment.

"I know it sounds like a cliché, but you really don't think it will ever happen to your child. It felt like our world fell out from under us. During those first few weeks I remember wondering if this was it, I was taking so many photos of us together and wondering if it could be the last." Said Harri, Eddie's mum.

Eddie was put onto a treatment plan that included eight months of intense chemotherapy, followed by two and a half years of maintenance treatment. As part of his treatment at GOSH Eddie's family were also offered WGS to identify any cancer-causing changes.

"When we were offered whole genome sequencing, we didn't even hesitate. I wanted to have all the information, I wanted to have some peace of mind for the future and know that Eddie was having the right care throughout. I also wanted to make sure that Eddie's brother, Leo, wasn't any more likely to get T-ALL because Eddie had." Said Harri, Eddie's mum.

On his seventh birthday, Eddie's family received the call to say he was in remission. Now, at nine years-old Eddie is nearing the end of his maintenance treatment and is doing well.

"We are trying to live each day, and this experience has really changed our outlook on life. We always try to take the positive from every situation. Words can't explain what Eddie has been through this past three years but he has come out the other side as a sensitive, confident, and smart young man. He is mature beyond his years and he has been involved in everything, including decisions about his treatment. To say we are proud, doesn't even come close to how we truly feel about him." Said Harri.

Their personal experience of WGS was so important on their journey that they provided support for this research.

"I always say that having a child with a cancer diagnosis feels like you've been standing on a trap door all these years without knowing. Then after the diagnosis, you are in freefall. And even when things are stable again, you are constantly aware that the trap door is still there and there is a possibility it could open again at any time. Having access to whole genome sequencing gave us some sense of reassurance, it could have informed us about targeted treatments and gave us some insight into future risk. We wanted to support something that had the potential to have a real impact on treatment and outcomes so when we heard about this research project and its potential, it was very exciting that we could be a small part of it. It helped us turn something so devastating into something positive and we just hope that this research helps." Said Harri.