A simple blood test may be used to diagnose five types of cancers – colon, lung, breast, stomach and womb – at early stages, scientists say. Researchers from National Institute of Health (NIH) in US have identified a striking signature in tumour DNA that occurs in these types of cancers.
They also found evidence that this methylation signature may be present in many more types of cancer. The specific signature results from a chemical modification of DNA called methylation, which can control the expression of genes like a dimmer on a light switch.
Higher amounts of DNA methylation (hypermethylation), like that found by researchers in some tumour DNA, decreases a gene’s activity. Based on this advance, researchers hope to spur development of a blood test that can be used to diagnose a variety of cancers at early stages, when treatments can be most effective.
“Finding a distinctive methylation-based signature is like looking for a spruce tree in a pine forest. It is a technical challenge to identify, but we found an elevated methylation signature around the gene known as ZNF154 that is unique to tumours,” said Laura Elnitski from NIH.
For the study, researchers developed a series of steps that uncovered telltale methylation marks in colon, lung, breast, stomach and endometrial cancers. They showed that all the tumour types and subtypes consistently produced the same methylation mark around ZNF154.
“Finding the methylation signature was an incredibly arduous and valuable process. These findings could be an important step in developing a test to identify early cancers through a blood test,” said Dan Kastner from NIH. Researchers sequenced the tumour DNA that had been amplified using a technique called polymerase chain reaction (PCR). They then analysed the results, finding elevated levels of methylation at ZNF154 across the different tumour types.
To verify the connection between increased methylation and cancer, they developed a computer programme that looked at the methylation marks in the DNA of people with and without cancer.
By feeding this information into the programme, they were able to predict a threshold for detecting tumour DNA. Even when they reduced the amount of methylated molecules by 99 per cent, the computer could still detect the cancer-related methylation marks in the mixture.
Knowing that tumours often shed DNA into the bloodstream, researchers calculated the proportions of circulating tumour DNA that could be found in the blood, researchers said.
The findings were published in The Journal of Molecular Diagnostics.
