New research led by scientists at the Wellcome Trust Sanger Institute in Cambridge, and part-funded by Breakthrough Breast Cancer, has provided unique insight into the genetic drivers behind breast cancer.
This latest chapter in a long-running genetics research project has now established a key genetic disruption as a potential driver behind the signatures of genetic mutations common to breast cancer, providing new insight into the root causes of the disease.
These findings build upon past research by the team, which demonstrated that all human cancers shared 21 genetic signatures, significantly advancing our understanding of the genetic processes that contribute to the development of cancer. Interestingly, whilst some of these signatures were common to all cancers, others were restricted to single types.
Each of these signatures were created by specific types of genetic mutation which could be attributed to external sources such as UV exposure or even as a result of normal cellular processes. Upon closer analysis, the team were able to identify that the two signatures strongly associated with breast cancer were likely to be caused by mutations induced by a group of enzymes called APOBEC3.
The APOBEC3 enzymes are able to edit and modify DNA as part of their normal function to control the production of antibodies against viral infections, offering some explanation as to how these enzymes may cause changes to DNA that lead to cancer. These enzymes are coded for by the APOBEC3 gene cluster – a group of genes that sit next to each other within the genetic code - and interestingly, women with part of this cluster deleted from their genome seem to be at higher risk of breast cancer.
This new analysis of the cancer genomes from breast cancer patients has now revealed that patients with a deletion within the APOBEC3 gene cluster are much more likely to have a breast cancer with the two genetic signatures most associated with the disease. This adds weight to the mounting evidence that disruption of APOBEC3 enzymes could be responsible for the underlying genetic processes which cause many cases of breast cancer.
This research has implications far beyond breast cancer as the two genetic signatures caused by this deletion are also highly prevalent in a spectrum of other cancers. We don’t yet know why disruption of these enzymes leads to these signatures but if we can pinpoint and understand the mechanism at play here, it could have a major impact on how we both prevent and treat cancer in the future.
Senior Research Officer at Breakthrough Breast Cancer, Dr Matthew Lam, said:
“We knew that a deletion in the APOBEC3 gene cluster seemed to be linked to an increased risk of breast cancer, but until now it was unclear how this was associated to the genetic signatures common across breast cancers.
“We still don’t know exactly why blocking the disruption of APOBEC3 enzymes leads to the development of breast cancer, but this research has taken a huge step towards understanding how and why this relationship occurs which has much wider implications for cancer prevention and treatment as a whole.”
These findings were published today in the journal Nature Genetics, and the research teams were led by Professor Mike Stratton – who famously helped discover the breast cancer gene BRCA2 with support from Breakthrough.