Immune system ‘friendly fire’ triggers HPV-linked cancer
Genes that usually help the body fight off viral infections could actually be involved in the development of certain cancers, UK research has shown.
"It's intriguing to see that the APOBEC genes may actually be hitting the wrong target" - Dr Sally Roberts, Cancer research UK
A collection of genes called the ‘APOBEC family’ normally slow the spread of viruses by attacking their DNA, preventing them from replicating.
They do this by causing changes to the virus’s DNA – known as mutations – which occur in recognisable patterns.
But new research from University College London (UCL), part-funded by Cancer Research UK, shows that these patterns can also be seen in the DNA of certain cancer cells, especially those triggered by infection with human papillomavirus (HPV). These include cervical cancer, anal cancer, and various forms of head and neck cancer.
The researchers believe that these DNA changes may be a form of ‘collateral damage’ caused by the body’s defence system – disrupting cell growth and ultimately leading to cancer.
Senior author Dr Tim Fenton, said: “Genes from the APOBEC family encode proteins that modify the DNA of invading viruses, causing mutations that prevent the virus from replicating.
“We have now shown that they can cause mutations in our own DNA after HPV infection, leading to cancer.”
Dr Sally Roberts, a Cancer Research UK expert in HPV-linked cancers, who was not involved in the research, said: "It's intriguing to see that the APOBEC genes, which normally protect cells against virus infections, may actually be hitting the wrong target in HPV-infected cells and triggering potentially cancer causing gene faults.”
Publishing their findings in the journal Cell Reports, the researchers found that the changes caused by the APOBEC proteins produced mutation ‘hotspots’ in a gene called PIK3CA.
This gene is involved in the regulation and growth of cells, and is associated with the development of multiple types of cancer.
Co-lead author Dr Stephen Henderson, said: “It is not clear why HPV infection causes the APOBEC genes to misbehave and mutate PIK3CA. It could be that the body responds to HPV infection with increased ABOBEC activity, simply making ‘friendly fire’ more likely.
“Alternatively, there may well be something about the virus that causes the APOBEC response to wrongly target the body’s own proteins for mutation.”
The researchers believe the findings could be used to identify patients with particular APOBEC genes that are linked to HPV cancer risk.
But more work is required to find out why the APOBEC genes seem to ‘misfire’ in infected cells, added Cancer Research UK’s Dr Roberts.
"This is an important contribution to our understanding of how infection with HPV may cause cancer, and the next steps will be to map the finer details of why this normally protective mechanism misfires."
The research was funded by the Rosetrees Trust, Cancer Research UK and the Debbie Fund.
Copyright Press Association 2014
- Henderson S, et al. (2014). APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development, Cell Reports, DOI: 10.1016/j.celrep.2014.05.012