Blood cancer analysis could lead to more targeted patient care
A new method for risk stratifying patients with chronic lymphocytic leukaemia could allow healthcare professionals to better guide their treatment plans for improved patient outcomes.
Researchers from the School of Medicine have been involved in a collaborative national study, led by the University of Oxford, as part of the UK’s 100,000 Genomes Project. The study is one of the largest and most comprehensive analysis of the genomic landscape of the most common type of blood cancer, chronic lymphocytic leukaemia (CLL).
Published in the journal Nature Genetics, the study analysed CLL and defined five genomic subgroups, associating them with clinical outcomes. The subgroups provide a better estimation of patient prognosis, which could lead to more tailored patient care.
Researchers 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.
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?”
Anna Hockaday, Operations Director, Leeds Institute of Clinical Trials Research, said: “This work is the outcome of an extensive national collaboration and shows the importance of safely sharing high quality data from clinical trials to improve our understanding of cancer biology. These findings will inform our future clinical trials to make sure patients with CLL get the treatments which are best for them.”
This study paves the way for routine clinical application of whole genome analyses for risk stratification in other cancer types. The analysis also identified 148 new putative genetic drivers of CLL, and future research on these drivers may uncover new mechanisms in CLL initiation and progression, with the potential for the development of novel therapeutics.