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Genetic ‘signature’ points to poor blood cancer outcome

Testing for a DNA signature could predict which patients with myeloma – a cancer of immune cells in the blood and bone marrow – are likely to develop more serious disease, with a reduced chance of survival. 

A team at The Institute of Cancer Research, London, found that cancer cells with the signature gain more DNA mutations than those without. 

These mutations make the cancer more genetically complex, and more likely to evolve into treatment-resistant forms.

The study, published in Nature Communications, used genetic sequencing to analyse all of the genes of 463 patients with myeloma.

It searched for a genetic signature caused by a molecule called APOBEC, which edits DNA code in healthy immune cells to create the genetic diversity that allows them to adapt to threats from infection. 

The molecule edits in a particular way, leaving a distinctive pattern that can be picked up by researchers through genetic sequencing.

The new study shows that APOBEC molecules become overactive in myeloma, or act on genes that they are not supposed to – leading to more advanced cancer. Eighteen of the patients analysed in the study had the APOBEC signature in their cells.

Along with the APOBEC signature, the researchers discovered that a number of other DNA and chromosome mutations were associated with more severe forms of the disease – including the common cancer gene, MYC. 

The study was funded by Myeloma UK, Cancer Research UK and the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR.

Study leader Professor Gareth Morgan, who conducted the research as Professor of Haematology at the ICR, said: 

“The treatment of myeloma has improved in recent years – but there are still a significant number of patients who succumb to the disease. Our research has identified, for the first time, several genetic features that indicate which patients are at high risk of developing more advanced cancer.

“In the future we hope to be able to use this information to test for patients most at risk, and be able to target specific treatment to their individual needs, bolstering their chance of survival.” 

Eric Lowe, Chief Executive of Myeloma UK, said: “Adapting the current one-size-fits-all approach to treatment is critically important to ensure myeloma patients only receive treatment that is stratified to the specific nature of their disease and which has a high probability of working. We are grateful to the myeloma research team at the ICR for their hard work and dedication and are very proud that our programme grant is being used to fund such high-quality research, producing data that patients will benefit from in the clinic.’’


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