Whole genome sequencing may improve clinical care of childhood cancer

Whole genome sequencing has improved the clinical care of some children with cancer in England, 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 efforts to provide genome sequencing to all children with cancer and shows how it can improve care management in real-world time, providing more benefits than all current tests combined.

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

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

Additionally, in 29 percent of cases, genome sequencing provided additional information that helped clinicians better understand individual children’s tumors and informed future management. For example, the discovery of unexpected mutations that increase future cancer risk leading to preventive measures such as regular screening.

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

Whole genome sequencing (WGS) is a single test that provides a complete readout of a tumor’s entire genetic code and identifies every cancer-causing mutation. By comparison, traditional standard-of-care tests only look at tiny areas of the cancer genome, and therefore require many more tests per child.

Whole genome sequencing provides the gold standard, the most comprehensive and cutting edge of cancer. What was once a research tool that the Sanger Institute began exploring 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 in healthcare enabling us to provide better, personalized care for children with cancer.”

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

NHS England is one of the few health services in the world to have 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 to support its use, whole genome sequencing of cancer is not yet a 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 at two English units where this gold standard test is regularly provided.

The team analyzed the clinical and diagnostic information in these units and evaluated how genome sequencing affected the care of children with cancer.

They found that WGS changed clinical management in seven percent of cases, improving care for 20 children by providing information that cannot be obtained from standard care tests.

In addition, WGS faithfully reproduced each of the 738 standard-of-care tests used in these 281 cases, suggesting that a single WGS test could replace the multiple tests currently used by the NHS if it proves to be economically viable.

WGS provides a detailed picture of rare cancers, for example by revealing new cancer variants. Widespread use of genome sequencing will enable clinicians to access this knowledge about individual patients, while simultaneously building a powerful shared genomic resource for research into new treatment targets, potential prevention strategies, and the origins of cancer.

Dr Jack Bartram, senior author from Great Ormond Street Hospital NHS Foundation Trust and North Thames Genomic Medicine Service, said: “The treatment of childhood cancer is mainly driven by genetic characteristics of the tumor and therefore an in-depth genetic understanding of cancer is vital. in guiding our practice, our research shows that whole-genome sequencing offers tangible benefits over existing tests, providing better care for our patients. Cancer.”

Eddie’s story

When he was six years old, Eddie began to have regular low-grade fevers that seemed to take a toll on him. Although early tests came back normal, fevers became more frequent and his mum, Harry, 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 in Eddie’s chest and he was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL). Eddie was immediately taken 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 had collapsed beneath us. Those first few weeks I remember wondering if this was it, I was taking so many pictures with us and wondering if it could be the last one,” said Harry, Eddie’s mom.

Eddie entered a treatment program that included eight months of intense chemotherapy, followed by two and a half years of maintenance therapy. As part of his treatment 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 had the right care throughout. I also wanted to make sure that Eddie’s brother Leo didn’t have a better chance of getting T-ALL because Eddie had.” Harry, Eddie’s mom, said.

On his seventh birthday, Eddie’s family got the call to say he was in remission. Now, at nine, Eddie is nearing the end of maintenance therapy and doing well.

“We try to live each day and this experience has really changed our outlook on life. We always try to take the positive out of every situation. Words cannot explain what Eddie has been through in the last three years, but he has come out the other side as a sensitive, confident and intelligent young man who is mature beyond his years and has been involved in everything, including decisions about his treatment, doesn’t even come close to how we really feel about him,” said Harry.

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

“I always say that having a child diagnosed with cancer is like standing in a trap all these years without knowing it. After the diagnosis, you’re in free fall. And even when things are stable again, you’re constantly Knowing that the trap door is still there and there’s a chance it could open again at any moment Access to whole genome sequencing gave us some sense of reassurance, it could have informed us about targeted therapies and given us some insight into future risks .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 something so disruptive and hopefully just this research to help,” said Harry.