A cancer screening program that predicts tumors decades before they develop could be on the horizon.
Scientists have identified a link between the risk of the disease and clusters of chemicals in an individual’s cells.
Known as circular RNAs, they are bits of DNA that deliver messages to proteins.
The breakthrough offers hope of developing personalized vaccines for vulnerable patients.
Lead author Professor Simon Conn, of Flinders University in Australia, said: “Environmental and genetic factors have long been believed as the major contributors to cancer.”
“We call this revolutionary finding ‘ER3D’ – from endogenous RNA directed DNA damage, it ushers in an entirely new area of medical and molecular biology research.”
“This is the first example of a genetic molecule present within many of us that has the capacity to cause mutation and drive cancer from inside.”
“This possibility opens the door for using these molecules as markers of disease at a very early stage, where the likelihood of curing cancers is much higher.”
The study showed specific circular RNAs within many of us can stick to the DNA in our cells and cause mutations that result in cancer – known as oncogenes.
It compared neonatal blood tests, or “Guthrie cards,” of babies who went on to develop acute leukemia as infants.
One specific circular RNA was present at much higher levels at birth, prior to onset of symptoms, compared to peers with healthy blood.
The findings suggest it is the abundance of the circular RNA molecules which is a major determinant for why some develop these specific oncogenes and others do not.
Conn said: “These specific 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”.
“This repair is not always perfect and this can result in small mutations, like a misspelled word within a book, or worse, very, very large and devastating mutations”.
“With the circular RNAs also able to alter the physical location of the broken DNA within the cell nucleus, two distinct regions of the DNA can be stuck together during the repair process – like the ripping of two different books and sticking them together.”
Multiple circular RNAs appear to act in partnership, causing breaks at multiple sites in the DNA.
Lead author Dr. Vanessa Conn explained: “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.”
“This was demonstrated in two different cell types, and it was found that this drove the rapid onset of aggressive leukemia.”
Gene fusions arising from circular RNAs are at well-known ‘hotspots’ of mutation in leukemia, say the husband and wife team.
This is an important consideration in Australia which has the highest incidence in the world, with around 35,000 currently living with the disease.
These gene fusions have been used by doctors around the world for many years in guiding treatment options as they are known to worsen the prognosis for the patient who carries them.
However, until now it was unknown how these mutations arose even though more than 100 known fusions were found in patients.
Dr. Conn said: “Not surprisingly, it is not only leukemia where the process of ER3D occurs.”
“We now have evidence that ER3D is not restricted only to leukemia but to other cancers and human diseases.”
The researchers are continuing to investigate circular RNAs role in cancer and other diseases.
The study was published in the Journal Cancer Cell.
Produced in association with SWNS Talker
Edited by Daisy Atino and Deborah .C. Amirize
