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

All children with cancer should be offered whole genome sequencing, say researchers who have led the first study into its impact in the NHS.

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

NHS England is one of the few health services in the world to offer universal genomic sequencing to every child with suspected cancer, through the Genomic Medicine Service. However, standard tests only look at tiny regions of the cancer genome, meaning multiple tests are often needed for each child.

Whole genome sequencing (WGS) is a unique test that provides a complete readout of a tumor’s entire genetic code, identifying every cancer-causing mutation.

Numerous barriers and a lack of real-time practice evidence supporting its use have so far prevented its widespread adoption.

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The new research, led by 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 in two English units where WGS is routinely performed.

Researchers found that this single test offered more benefits than all current tests combined.

They found that WGS changed clinical management in seven percent of cases, meaning it improved the care of 20 children in the study, by providing information that was not possible from standard-of-care tests.

The WGS provided data acquired by each of the 738 standard of care tests in these 281 cases, suggesting that a single WGS test could replace the current use of multiple tests in the NHS, if proven economically viable.

In 29% of cases, WGS provided additional information that helped clinicians better understand each child’s tumors and inform future management. For example, it helped discover unexpected mutations that increase the risk of future cancer, allowing preventative measures, such as regular screening, to be taken.

Professor Sam Behjati, lead author from the Wellcome Sanger Institute, Cambridge University Hospitals and the University of Cambridge, said: “Whole genome sequencing provides the gold standard, the most comprehensive and cutting-edge view of cancer.

“What was once a research tool that the Sanger Institute began exploring over a decade ago has now become a clinical test that I can offer to my patients.

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“This is a powerful example of the genomic data revolution in healthcare, enabling us to provide better, more individualized care to children with cancer.”

The study, published yesterday (July 2) in Nature Medicine, suggests that widespread use of WGS will also help create a powerful shared genomic resource for research into new treatment targets, possible prevention strategies and the origins of cancer.

Dr Jack Bartram, lead author from Great Ormond Street Hospital NHS Foundation Trust and North Thames Genomic Medicine Service, said: “Treatment of childhood cancer is primarily driven by the genetic characteristics of the tumour. Therefore, a thorough genetic understanding of cancer is essential to guide our practice.

“Our research shows that whole genome sequencing offers tangible benefits over existing tests, enabling us to better care for our patients. We hope this research will really shine a light on why whole genome sequencing should be offered as part of routine clinical care to all children with suspected cancer.”

Among the children in the study was Eddie, who began having regular low-grade fevers that seriously affected him by the age of six. Initial 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 when 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 leukaemia (T-ALL). Eddie was immediately transferred to Great Ormond Street Hospital (GOSH) to begin treatment.

“I know it sounds cliché, but you can’t really believe that this is going to happen to your child. It was like our world was falling apart,” Harri said. “Those first few weeks I wondered if this was the end, I was taking so many pictures of us together and wondering if this would be the last.”

Eddie underwent a treatment plan that included eight months of intense chemotherapy, followed by two and a half years of maintenance therapy.

As part of his treatment at GOSH, Eddie was offered a 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,” Harri said. “I wanted peace of mind for the future and to know that Eddie would receive the right care throughout his journey. I also wanted to make sure that Eddie’s brother, Leo, wouldn’t be at a higher risk of developing T-ALL because Eddie had it.”

On his seventh birthday, Eddie’s family received a call that he was in remission. Today, at age nine, Eddie is about to finish his maintenance treatment and is doing well.

“We try to live each day and this experience has really changed our outlook on life. We always try to find the positive in every situation. Words can’t explain what Eddie has been through these last three years, but he has come out of it a sensitive, confident and intelligent young man.

“He is mature for his age and 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,” Harri said.

“I always say that having a child with a cancer diagnosis is like being in a trapdoor all these years without knowing it. Then, after the diagnosis, you’re in a tailspin. And even when things stabilize again, you’re constantly aware that the trapdoor is still there and could open again at any moment.

“Having access to whole genome sequencing gave us peace of mind. It could have informed us about targeted treatments and given us insight into future risks.

“We wanted to support a project that could have a real impact on treatment and outcomes. When we heard about this research project and its potential, we were very excited to be able to be involved. It has helped us turn something so devastating into something positive and we just hope that this research will help us.”