Research news // 12th September 2019
Researchers at The Institute of Cancer Research, London, have identified the major biological processes which cause the genetic changes (mutations) involved in the early development of myeloma.
The research, largely funded by the Myeloma UK Translational Research Programme, improves our understanding of why myeloma develops and how it evolves. It will also help to drive improved prognosis and develop more personalised treatments for myeloma patients.
Myeloma is a blood cancer characterised by abnormal plasma cells in the bone marrow. It is caused by mutations in the DNA of plasma cells. Although the common genetic abnormalities found in myeloma cells have been identified, the biological processes causing these mutations are not fully understood.
These abnormalities differ between patients, and the type of abnormality affects how a patient’s myeloma presents and responds to treatment. Where it is possible to group patients by genetic profile, it becomes easier to define patient prognosis and risk status.
Mutations to the DNA in our cells occur throughout our lifetime. There are many reasons these mutations occur and most mutations are harmless. However, some of these mutations will be involved in the development of cancer.
By studying the patterns of mutations (mutational signatures) present in cancer cells, researchers have learnt more about the biological processes contributing to the development and evolution of cancer.
To understand more about the biological process involved in the development of myeloma, the team at The Institute of Cancer Research (ICR) studied genetic data of over 800 myeloma patients collected as part of the CoMMpass trial. The team analysed the results from whole-genome sequencing (WGS) and whole-exome sequencing (WES) to identify and map out which mutational signatures, involved in the development of cancer, were also found in myeloma cells.
The results showed that mutational signatures linked to four main biological processes account for around 80% of all mutations in myeloma. These processes were:
- Errors in DNA copying and repair processes
- Dysfunction of the activation-induced deaminase (AID) proteins
- Dysfunction of apolipoprotein B editing complex (APOBEC) proteins.
AID and APOBEC proteins are enzymes involved in the editing of DNA and RNA whose dysfunction has been associated with the development of cancer.
Findings suggest that mutational signatures could play a role in helping identify high-risk myeloma patients and predicting patient outcomes.
Professor Richard Houlston, Head of the Division of Genetics and Epidemiology at the ICR, said:
“Understanding of the genetics of myeloma plays a key role in identifying why myeloma is such a complex and individual cancer. This research helps improve our knowledge of the processes causing the disease and refine patient outcome.
With continued funding support from Myeloma UK we aim to learn more about how myeloma develops and evolves. We are performing state of the art molecular analyses to uncover how genetic mutations impact gene function. This information should unlock the key processes defining disease relapse paving the way for novel therapeutic interventions.”
Dr Karthik Ramasamy, Consultant Haematologist at Oxford University Hospitals and Director of the Board at Myeloma UK said:
“We are pleased to see the results from research largely funded by our Translational Research Programme, helping to understand how and why myeloma develops. Increasing our knowledge of the complex pathways driving the development and progression of myeloma is going to be key to identifying new myeloma therapies, and to enable the tailoring of patient treatments. This data will also contribute to the planning of studies to better understand MGUS and smouldering myeloma where there is now a considerable clinical research interest“
Learn more about genetics and myeloma: