4 November 2022
- The University of Oxford has led the largest and most comprehensive analysis of the entire genomic landscape of the commonest type of blood cancer called chronic lymphocytic leukaemia (CLL) as part of the UK’s 100,000 Genomes Project
- This work defines five genomic subgroups of CLL and associates these with clinical outcomes
- These subgroups provide a better estimation of patient prognosis than achieved by previous single gene analyses, allowing more tailored patient care
- This study demonstrates the potential for routine clinical application of genome-wide analyses for other cancer types.
A collaborative study led by the University of Oxford as part of the UK’s 100,000 Genomes Project, published in Nature Genetics today, has defined five new subgroups of the most common type of blood cancer, chronic lymphocytic leukaemia (CLL) and associated these with clinical outcomes. This new method for risk stratifying patients could lead to more personalised patient care.
This is the first study to analyse all the relevant changes in DNA across the entire cancer genome, rather than targeted regions, to classify patients with cancer and link these subgroups to clinical outcomes.
Professor Anna Schuh, Department of Oncology, University of Oxford who led the study said: ‘We know that cancer is fundamentally a disease caused by changes in DNA that are acquired over the lifetime of an individual. The lab tools we currently use to predict whether or not a patient is likely to respond to a given therapy usually focus on single abnormalities in the cancer DNA and do not accurately predict the patient’s clinical outcome. This is why we asked the simple question: can we increase the precision of current testing by looking at all the acquired DNA changes in cancer at once?’
This study analysed the entire genome sequences1 from 485 patients with CLL who were enrolled in national clinical trials led by the Universities of Liverpool and Leeds, provided samples for the UK CLL Biobank in Liverpool and consented for their samples to be used in the 100,000 Genomes Project run by Genomics England. By comparing the whole genome sequencing data from the cancer and healthy tissues in these patients, the team were able to map known and newly identified DNA changes, structural alterations, cancer mutational signatures and other global measures associated with CLL throughout the genome. They identified 186 distinct and recurrent genomic alterations and used these to define five genomic subgroups of CLL that associate with different clinical outcomes.
Following additional validation in patients receiving a wider range of treatments than those included in this study, particularly targeted therapies, these new genomic subgroups for CLL could be used to better guide the selection of therapies for improved patient outcomes.
This study paves the way for routine clinical application of whole genome analyses for risk stratification in other cancer types.
The team’s analysis also identified 148 new putative genetic drivers of CLL. Future research on these drivers may uncover new mechanisms in CLL initiation and progression, with potential for the development of novel therapeutics.
Professor Sir Mark Caulfield, Vice Principal for Health for Queen Mary University of London and former Chief Scientist and lead of the 100,000 Genomes Project at Genomics England said: ‘This is the largest international genomic analysis of this blood cancer, which excitingly demonstrates the real value of whole genome sequencing from the 100,000 Genomes Project. It also harnesses the high-quality blood cancer samples from the Liverpool Chronic Lymphocytic Leukaemia Biobank and associated clinical data collected by the Clinical Trial Units at Liverpool and Leeds universities as part of multi-centre National Cancer Research Institute-supported clinical trials.
Our work shows that the entire genome is superior in classifying patients into groups compared to the conventional targeted approaches and that we can predict response to treatment more precisely and in more patients.’
Professor Andrew Pettitt, founding Director of the UK CLL Biobank and Chief Investigator for two of the contributing clinical trials, said: ‘This ground-breaking study is a paradigm for what can be achieved through a nationally coordinated approach to collaborative working that allows the application of cutting-edge science to a large number of high-quality samples obtained from uniform, well-defined patient cohorts and linked to high-quality clinical outcome data.’
Jackie Martin, patient representative for the Genomics England haematology project commented: ‘A new CLL patient classifier would allow patients of the future to be offered the best treatment first time according to their CLL subgroup, saving unnecessary treatments with potentially toxic side effects. It will also aid in selecting the most appropriate patients for trials of new, targeted therapies. This work has a potentially huge, positive impact on patients with CLL and importantly demonstrates the feasibility of this approach in other cancer types.’
Notes for editors:
For further information or to arrange an interview, please contact Christopher McIntyre, University of Oxford press office at firstname.lastname@example.org or on +44 (0)1865 270046.
Interview opportunities are available with:
- Professor Anna Schuh, Professor of Molecular Diagnostics at the Department of Oncology, University of Oxford and Honorary Consultant Haematologist at Oxford University Hospitals NHS Foundation Trust, who led the study.
This new paper, ‘Whole genome landscape of chronic lymphocytic leukaemia and its association with clinical outcome’ is published on Friday 4th November 2022 at 16:00 GMT in Nature Genetics at http://dx.doi.org/10.1038/s41588-022-01211-y
This study was led by Professor Anna Schuh, Professor of Molecular Diagnostics at the Department of Oncology, University of Oxford and Honorary Consultant Haematologist at Oxford University Hospitals NHS Foundation Trust. It was supported by the National Institute for Health and Care Research, NHS England, the Wellcome Trust, Cancer Research UK, the Medical Research Council and Blood Cancer UK.
1Genomic sequencing is the analysis of a person’s entire genome, the 3.2 billion letters of their DNA that contain the instructions for making and maintaining their body. It’s used by doctors and scientists to identify genetic changes causing specific diseases and conditions. The findings can then be used in the development of personalised treatments and care plans, based on an individual’s unique genome.
About Oxford Cancer
Oxford University’s cancer research is managed through Oxford Cancer: a city-wide network and partnership between Oxford University and Oxford University Hospitals NHS Trust based on the University’s Translational Biomedical Research Campus.
With over 1,000 cancer research scientists spread across the city and beyond, Oxford is ideally placed to enable and combine the best research and clinical resources in order to innovate cancer treatment and care worldwide. Learn more at www.cancer.ox.ac.uk
About Oxford University
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the seventh year running, and number 2 in the QS World Rankings 2022. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer.
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About Genomics England
Genomics England (https://www.genomicsengland.co.uk) is a global leader in advancing and delivering genomic medicine at scale, for all. Building on our delivery of the 100,000 Genomes Project, we are today enabling the world's first national Whole Genome Sequencing service in the NHS Genomic Medicine Service, delivering the most advanced genomic healthcare today.
We maximise the patient and participant benefit of this service by using the same trusted and proven infrastructure and expertise, and consent and governance framework, to support the development of the genomic medicine of tomorrow, together with the NHS, industry, and academia. All this focused on delivering our vision of a world in which everyone benefits from genomic medicine.
About the UK CLL Biobank
Funded by Blood Cancer UK since 2008, the UK CLL Biobank was established as a national resource to drive and facilitate translational research in CLL. Based at the University of Liverpool and overseen by a multistakeholder Governance Committee, the biobank contains samples from >2400 patients recruited into 12 national clinical trials and has supported research projects at laboratories around the UK. It was selected as a case study for collaborative working by the National Cancer Research Institute.
About the National Cancer Research Institute (NCRI)
The National Cancer Research Institute (NCRI) is a UK-wide partnership of cancer research funders, established in 2001.
NCRI works to coordinate research related to cancer, to improve the quality and relevance of research and to accelerate the translation of research into clinical practice for the benefit of patients.
The NCRI Groups bring the cancer research community together to develop practice-changing research, from basic to clinical research and across all cancer types.
For more information visit www.ncri.org.uk