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All children with cancer should be offered whole genome sequencing, say researchers at Wellcome Sanger Institute, University of Cambridge and Great Ormond Street





All children with cancer should be offered whole genome sequencing, says researchers, who have conducted the first study of its impact in the NHS.

They found that the method - described as the gold standard in sequencing technology - had improved clinical care in some cases, uncovered useful extra information and reduced the number of tests required.

Dr Sam Behjati, a consultant paediatric oncologist at CUH and group leader at the Wellcome Sanger Institute
Dr Sam Behjati, a consultant paediatric oncologist at CUH and group leader at the Wellcome Sanger Institute

NHS England is one of the few health services in the world with a national initiative, through the Genomic Medicine Service, that offers universal genome sequencing to every child with suspected cancer. However, the standard tests only look at tiny regions of the cancer genome, meaning many tests are often required for each child.

Whole genome sequencing (WGS) is a single test providing a complete readout of the entire genetic code of a tumour, which identifies every single cancer-causing mutation.

Multiple barriers and a lack of evidence from real-time practice supporting its use have so far prevented it being widely adopted.

The new research, from the Wellcome Sanger Institute, Cambridge University Hospitals NHS Trust, Great Ormond Street Hospital and the University of Cambridge, involved 281 children with suspected solid cancers or leukaemia across two English units where WGS is provided regularly.

The researchers found this single test provided more benefits than all the current tests combined.

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

WGS provided the data that was acquired by every one of the 738 standard of care tests in these 281 cases, which suggests a single WGS test could replace the current use of multiple tests in the NHS, if it is shown to be economically viable.

Preparatory work and analysis of WGS reports carried out at Cambridge Genomics Laboratory. Picture: Cambridge University Hospitals
Preparatory work and analysis of WGS reports carried out at Cambridge Genomics Laboratory. Picture: Cambridge University Hospitals

In 29 per cent of cases, WGS provided additional information that helped clinicians better understand the tumours of individual children and informed future management. It uncovered, for example, unexpected mutations that increase future cancer risk, enabling preventative measures to be taken, such as regular screening.

Prof Sam Behjati, senior author from the Wellcome Sanger Institute, Cambridge University Hospitals, and the University of Cambridge said: “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, individualised care for children with cancer.”

The study, published yesterday (2 July) in Nature Medicine, suggests widespread use of WGS will also help build 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 was given whole genome sequencing following diagnosis with T-cell acute lymphoblastic leukemia
Eddie was given whole genome sequencing following diagnosis with T-cell acute lymphoblastic leukemia

Among the children in involved in the study was Eddie, who began to have regular low-grade fevers that badly affected him from the age of six. Early tests came back normal, but the fevers became more frequent and his mother, Harri, noticed that on one or two occasions he seemed out of breath even while doing something simple 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,” said Harri. “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.”

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 was 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,” said Harri. “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.”

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 these 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.

“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.”



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