APOBEC3B is an enzymatic source of mutation in breast cancer

The finding could lead to new ways to diagnose and treat breast cancer, exploiting the root cause of genetic damage - 'DNA editing' by the enzyme - rather than the damage itself.

Under normal circumstances, APOBEC enzymes help repair damaged DNA and protect against viruses like HIV.

But the University of Minnesota researchers showed in a research paper published in Nature that one particular form of APOBEC was found in high levels in breast cancer cells.

Lead researcher Dr Reuben Harris and his team measured the activity of seven related enzymes known collectively as the APOBEC3 family, in breast cancer cells grown in the lab and breast tumour samples.

They found that only one, known as APOBEC3B, was present in high levels inside cancer cells.

But APOBEC3B appears to be a biological "double-edged sword", as it protects some cells from viruses such as HIV, yet can produce changes giving rise to cancer in others.

In 2009, researchers funded by Cancer Research UK found evidence that a related enzyme, called AID, could similarly edit breast cancer DNA when activated by oestrogen.

And adding to the picture, last year researchers at the Wellcome Trust Sanger Institute in Cambridge published a detailed analysis of the DNA damage in breast cancer, and spotted signs that looked like the activity of APOBEC enzymes.

"Our next steps will focus on the connections between high levels of APOBEC3B, age and other genetic risk factors that are known breast cancer markers," said Dr Harris, who stressed the need for additional research.

"Ultimately, we hope our discovery leads to better therapeutic outcomes for patients."

In 2010, about 50,000 women and 400 men in the UK were diagnosed with breast cancer, and there were nearly 12,000 deaths from the disease.

If future studies confirm that high APOBEC3B levels indicate the early presence of breast cancer, a simple blood test could be a strategy for early detection.

Cancer Research UK's Professor Charlie Swanton, who studies the genetic complexity inside tumours, said it was a "fascinating and important study" which showed how researchers are beginning to understand the precise mechanisms that drive the genetic chaos found in cancer cells.

"Pinpointing these mechanisms give us new avenues to try to limit this chaos, or maybe even exploit it to tip cancers over the edge.

"There's a long way to go before we get a handle on the cancer's true genetic complexity, let alone turn this into treatments to help patients," he added.

"But studies like this show that important and tangible progress is being made in understanding this disease."

Reference

1. Burns, M. B., Lackey, L. et al. (2013). APOBEC3B is an enzymatic source of mutation in breast cancer Nature DOI: 10.1038/nature11881

Keywords: APOBEC3B, breast cancer

8. 2. 2013 Cancer Research UK

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