New research shows that a specific form of genetic test – known as whole genome sequencing, or WGS for short – is invaluable in patients with a certain type of cancer that is difficult to diagnose and treat.
Sarcoma is a type of cancer that can appear anywhere in the body. Each year around 5,300 people in the UK are diagnosed with sarcoma. There are two main types: soft tissue sarcoma, which develops in connective tissue such as muscle, nerves, tendons and blood vessels, and bone sarcoma, which is much rarer.
The research study (opens in a new tab), published in the British Journal of Cancer, offered whole genome sequencing (WGS) as standard care to 67 patients who were undergoing treatment for sarcoma at Cambridge University Hospitals (CUH) NHS Foundation Trust over a two year period.
WGS changed the diagnosis in about one third of patients and enabled a third to be switched to a more personalised, targeted treatment. In contrast, the current standard of care identifies personalised therapies for around one tenth of patients.
Lead author of the research paper, Dr James Watkins, Molecular Pathology Clinical Lead for East Genomic Laboratory Hub (East GLH) said:
This study shows that whole genome sequencing is a game-changer for diagnosis and treatment of sarcoma patients. Diagnosis is particularly challenging because sarcomas are highly variable and non-sarcomatous tumours can also mimic sarcoma. It’s essential to get an accurate diagnosis to ensure optimal treatment, and current diagnostic approaches are often insufficient to do so. Sarcoma can also be challenging to treat and whole genome sequencing allows us to look at every gene in the cell to seek out potential personalised treatment options for patient benefit.
Dr James Watkins
In the study, whole genome sequencing changed the diagnosis for 25 of the 67 patients. For some patients, the genomic profile revealed by WGS suggested an alternative diagnosis that had not previously been considered. For 22 of our patients, WGS identified at least one potential target for personalised cancer therapy.
Whole genome sequencing (WGS)
Whole genome sequencing is a single test providing the entire genetic code of the tumour, identifying every single mutation. In contrast, traditional testing focuses on small, individual areas so more tests are often needed per patient.
Routine whole genome sequencing has recently been introduced by the NHS Genomic Medicine Service for all sarcoma patients. However, it is not yet used as standard of care across England.
CUH offers this treatment as standard of care, alongside the more traditional tests. This study highlights both the feasibility and significant benefits of offering WGS as standard for all sarcoma patients.
Dr Alona Sosinsky, co-author and Scientific Director for Cancer at Genomics England, said:
This publication is a further example of how implementation of whole genome sequencing as a clinical test within the healthcare system has unlocked so many exciting opportunities for precision oncology and moving further away from a one size fits all approach to cancer care for patients’ benefit. “The outcomes of the study will also contribute to continuously growing a national genomic research dataset, which offers one-of-a-kind insights that are helping genomic testing in this country go from strength to strength.
Dr Alona Sosinsky
Genomics England supported the study through its clinically accredited pipeline for the analysis and interpretation of WGS. Genomics England also provided access to data in the National Genomic Research Library (NGRL) - a database containing healthcare data and biological samples, established to facilitate future research. All the data held is de-identified, consented data from patients and participants through participation in research, such as the 100,000 Genomes Project, or NHS care.
Balwinder's story
Mr Balwinder Singh, 58 years old, from Bedford is one patient whose treatment and wellbeing has been transformed following whole genome sequencing. After starting chemotherapy for an aggressive form of soft tissue sarcoma cancer in September 2022, his disease progressed. He had whole genome sequencing in November 2022 with the aim of looking for new targets for his treatment due to the progression of his disease.
The WGS finding meant Mr Singh was eligible to get immunotherapy on compassionate grounds in April 2023. Mr Singh said:
The treatment that I have moved onto, thanks to whole genome sequencing, has transformed my life. It has given me a quality of life that I had not expected after being very ill for some time. My hair has grown back, eating is back to normal and I’ve put on weight – all due to my new treatment. I am now much more mobile around the house and able to drive again; I can drive myself to my hospital appointments, having been too weak to do this for some time. I was able to travel to India to see my family which wasn’t possible before.
Balwinder Singh
For Professor Serena Nik-Zainal, NIHR Research Professor of Genomic Medicine and Bioinformatics at the University of Cambridge, who was instrumental in Mr Singh’s treatment change, the detailed and comprehensive nature of WGS was crucial in identifying the more personalised treatments that have improved the quality of life for Mr Singh and other patients on the trial.
Professor Serena Nik-Zainal said: “Mr Singh had progressed on standard of care treatments but thanks to WGS, we were able to find the genetic signature of his cancer and switch him to his new immunotherapy treatment. In the UK, we have cancer WGS offered through the NHS Genomic Medicine Service - we should use this privileged position effectively, and perform cancer WGS clinical studies to gather the evidence to inform treatment decisions for our cancer patients. His case highlights just how important it is to offer WGS as standard to all sarcoma patients.”
Dr Jennifer Harrington, Consultant in Medical Oncology, Sarcoma, who was also involved in Mr Singh’s treatment, said: "He has had a fantastic response to immunotherapy. Without his WGS result, I would not have been able to apply for this treatment which has transformed his quality of life. Within three weeks of starting it, he no longer needed regular pain killers. His family are in India and he was previously so unwell that he would not have been able to travel. Now he’s fit enough to travel and enjoy time with them and his scans show he continues to respond to this treatment."
The research was a collaboration between NHS East Genomics Laboratory Hub, Cambridge University Hospitals NHS Foundation Trust, MRC Metabolic Diseases Unit, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, the National Institute for Health Research, the Cambridge Biomedical Research Centre, Royal National Orthopaedic Hospital and Genomics England.