Why do some people get cancer and not others? It might have to do with something that’s within us.

Australian cancer researchers have discovered the role played by circular RNA in causing cancer. These are a recently discovered family of genetic fragments present within our cells. 

The study, published in Cancer Cell, explains how specific circular RNAs within many of us can stick to the DNA in our cells and cause mutations which result in cancer. 

‘While environmental and genetic factors have long been believed the major contributors to cancer, this revolutionary finding – which we call ‘ER3D’ [endogenous RNA directed DNA damage] – ushers in an entirely new area of medical and molecular biology research,’ said Professor Simon Conn, one of the authors of the study.

‘This is the first example of a genetic molecule present within many of us which has the capacity to mutate our very own DNA and drive cancer from inside.’

These molecules could be the new therapeutic targets and markers of disease at a very early stage, when the likelihood of curing cancers is much higher.

Researchers compared the neonatal blood tests of babies who went on to develop acute leukemia as infants with children without any blood disorders. They found that one specific circular RNA was present at much higher levels at birth, prior to onset of the symptoms of leukemia.  

The findings suggest it is the abundance of the circular RNA molecules within certain individuals’ cells which is a major determinant for why they develop these specific cancer-causing genes or oncogenes and others do not.  

‘Circular RNAs can bind to DNA at many different locations across a range of cells. By binding to the DNA at specific sites, these circular RNAs cause a number of changes culminating in the breakage of the DNA which the cell must repair in order to survive,’ said Professor Conn.  

‘This repair is not always perfect and this can result in small mutations, like a misspelt word within a book, or worse, very, very large and devastating mutations.’

The circular RNAs were also able to alter the physical location of the broken DNA, like ripping up two different books and sticking them together.

Lead author Dr Vanessa Conn said multiple circular RNAs appear to act in partnership causing breaks at multiple sites in the DNA.  

‘This process, called chromosomal translocation, is a major problem for the cell as it results in gene fusions which can actually convert the cell from a normal cell into a cancerous cell,’ she said. 

‘This was demonstrated in two different cell types and it was found that this drove the rapid onset of aggressive leukemia.’

The gene fusions arising from the action of these circular RNAs are at well-known ‘hotspots’ of mutation in the blood cancer leukemia.

These gene fusions have been used by doctors around the world for many years in guiding treatment options as they are known to be a bad sign for patients who carry them, said the researchers.  

However, until now it was unknown how these mutations arose, even though more than 100 known fusions were found in patients. These functions were not limited to leukemia but also other cancers and human diseases which the researchers are studying further.

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