Researchers
have developed a test that could be used to diagnose all cancers. It is
based on a unique DNA signature that appears to be common across cancer
types.
The test has yet to be conducted on humans, and
clinical trials are needed before we know for sure if it can be used in
the clinic.
Each
cancer type, whether it be breast or bowel cancer, has different
genetic and other features. A test that detects one cancer may not work
on another. Researchers have long been looking for a commonality among
cancers to develop a diagnostic tool that could apply across all types.
Our research, published in the journal
Nature Communications, has
found that cancer DNA forms a unique structure when placed in water.
The structure is the same in DNA from samples of breast, prostate and
bowel cancers, as well as lymphoma. We used this discovery to develop a
test that can identify the cancerous DNA in less than ten minutes.
How our test works
Current
detection of cancer requires a tissue biopsy – a surgical procedure to
collect tissue from the patient’s tumour. Researchers have been looking
for a less invasive diagnostic test that can detect cancers at an
earlier stage. One possibility, still in development, is a liquid
biopsy, testing for circulating cancer DNA in the blood.
Our test also uses circulating cancer DNA but involves a different detection method.
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Nearly every cell in a person’s body has the same DNA, but
studies have found that cancer’s progression causes this DNA to undergo considerable reprogramming.
This
change is particularly evident in the distribution pattern of a tiny
molecule called a methyl group, which decorates the DNA.
A normal
cell DNA’s distinct methyl pattern is crucial to regulating its
machinery and maintaining its functions. It is also responsible for
turning genes on and off. Altering this pattern is one of the ways
cancer cells regulate their own proliferation.
This methyl
patterning has been studied before. However, its effect in a solution
(such as water) has never been explored. Using transmission electron
microscopy (a high-resolution microscope), we saw that cancerous DNA
fragments folded into three-dimensional structures in water. These were
different to what we saw with normal tissue DNA in the water.
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In the lab, gold particles are
commonly used
to help detect biological molecules (such as DNA). This is because gold
can affect molecular behaviour in a way that causes visible colour
changes. We discovered that cancerous DNA has a strong affinity towards
gold, which means it strongly binds to the gold particles.
This
finding directed us to develop a test that can detect cancerous DNA in
blood and tissue. This requires a tiny amount of purified DNA to be
mixed with some drops of gold particle solution. By simply observing the
colour change, it is possible to identify the cancerous DNA with the
naked eye within five minutes.
The test also works for
electrochemical detection – when the DNA is attached onto flat gold
electrodes. Since cancer DNA has higher affinity to gold, it provides a
higher relative electrochemical current signal in comparison to normal
DNA. This electrochemical method is highly sensitive and could also
eventually be used as a diagnostic tool.
Why this matters
For
this test to work properly the DNA must be pure. So far we have tested
more than 200 tissue and blood samples, with 90% accuracy. Accuracy is
important to ensure there are fewer false positives – wrongly detecting
cancer when there is none.
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The
types of cancers we tested included breast, prostate, bowel and
lymphoma. We have not yet tested other cancers, but because the
methylation pattern is similar across all cancers it is likely the DNA
will respond in the same way.
It is a promising start, though further analysis with more samples is needed to prove its clinical use.
The
next step is to do a large clinical study to understand how early a
cancer can be detected based on this novel DNA signature. We are
assessing the possibility to detect different cancer types from
different body fluids from early to later stages of cancer.
We are
also considering whether the test could help monitor treatment
responses based on the abundance of DNA signatures in body fluid during
treatment.
Abu Sina, Research Fellow, The University of Queensland, Laura G. Carrascosa, Postdoctoral Research Fellow, The University of Queensland and Matt Trau Professor, The University of Queensland.
This article first appeared on The Conversation.