A family of genes that normally combat viral infections interact with the human papillomavirus to cause cancer, researchers reveal today.
The virus is linked to cervical cancer and a range of other cancers. Young women are now offered a vaccine to protect them against the effects of the virus.
Researchers at University College London (UCL) have discovered that genes from the ‘APOBEC’ family cause mutations that can then lead to HPV-associated cancer.
Dr Tim Fenton, of the tumour virus team at the UCL Cancer Institute, has published a study in the latest edition of Cell Reports, which shows that the genes undergo very specific mutations.
“Genes from the APOBEC family encode proteins that modify the DNA of invading viruses, causing mutations that prevent the virus from replicating,” he said.
“We now provide evidence that they can also cause mutations in our own DNA after HPV infection, leading to cancer.”
More than 99% of cervical cancers are caused by HPV infection and although previous genetic studies have revealed links between APOBEC genes and cancer, this research shows that after HPV infection, APOBEC genes cause very specific mutations, with very high frequency in a cancer-promoting gene called PIK3CA, which leads to tumour development.
However, co-lead author Dr Stephen Henderson, of the Bill Lyons Informatics Centre at the UCL Cancer Institute, said it is not clear why HPV infection causes the APOBEC genes to mutate PIK3CA.
“It could be that the body responds to HPV infection with increased APOBEC activity, simply making ‘friendly fire’ more likely,” he said. “Alternatively, there may well be something about the virus that causes the APOBEC response to wrongly target the body’s own genes for mutation.”
The research team now hopes to learn what happens following HPV infection of cells in which APOBEC genes have been deleted.
“It will be interesting to see whether such APOBEC variants can predict the risk of developing cancer after HPV infections,” said Dr Fenton. “If at-risk groups could be identified by genetic testing, this could have important implications for HPV screening and vaccination programmes.”
Henderson S, Chakravarthy A et al. APOBEC-Mediated Cytosine Deamination Links PIK3CA Helical Domain Mutations to Human Papillomavirus-Driven Tumor Development. Cell Reports 6 June 2014.