Blood test for cancer

By filtering DNA fragments from the bloodstream, scientists have developed a highly accurate and sensitive test for cancer...

Cancer is a leading cause of death worldwide. Because earlier diagnosis is generally associated with better treatment outcomes, early detection of the disease is a priority. But before systematically screening for all cancers, doctors must consider the financial costs and the physical and emotional toll for the patient. The ideal situation would be to have a reliable and very sensitive test that is both cost-effectiveness and minimally invasive.

Now researchers at the Cancer Research UK (CRUK) Cambridge Institute, based at the University of Cambridge, think they are getting close with a new method of cancer testing that uses just a blood sample.

The approach relies on DNA released from cells into the bloodstream, usually when cells die naturally or are broken apart. This DNA is known as "cell-free DNA" and usually comprises short chunks or fragments of DNA produced as the genome is broken apart in dying cells. Critically, in patients with cancer, DNA from their tumour is present too.

Scientists can look for this by sequencing samples of the cell-free DNA in the blood. But the challenge is that “[DNA from healthy cells] is in a huge excess compared to the amount of faulty DNA that comes from the cancer cells,” explains James Brenton who led the new study, likening it to searching for “a DNA needle in a haystack.”

The breakthrough made by the Cambridge team was the discovery that circulating DNA fragments from tumours are, on average, much shorter than DNA fragments released from healthy cells. And if just the shorter pieces are extracted and studied, the detection rates for cancer climb rapidly. “With these new methods of, essentially, pulling out specific sizes, we can increase [detection of cancerous DNA] by over 2 fold in at least 95 percent of cancer patients and over 4 fold in about 10 percent of patients,” says Brenton.

Improved detection of tumour DNA has two main impacts. First, it allows detection of genetic changes, mutations or alterations in the number of copies of a certain gene; before the new size selection approach, such were changes were effectively undetectable. Meanwhile, machine learning algorithms trained to recognise circulating tumour DNA fragment characteristics may also teach us about the differences between the mutations found in tumours and random mutations occurring naturally in healthy cells.

Second, size selection allows detection of cancer sooner than is possible using either imaging or sequencing without selection. As result, “the patient may be better or fitter when we start treatment,” says Brenton. This is relevant for initial diagnosis, tracking response to cancer treatment and monitoring relapse.

This method is not restricted to a single cancer type and has been tested on eight forms of the disease. “Many of those cancers don't have easy ways of using other methods to detect or screen for them,” adds Brenton. 

In the future, size selection of cell-free DNA may be used to study cancer therapy. For example, as different cell death pathways produce different characteristic DNA fragments, this profile could provide insights into a drug’s mechanism of action. Additionally, associations between bacteria in the gut and treatment efficacy could be investigated by selectively sequencing the shorter bacterial DNA fragments in the blood. This technique may thus help overcome some of the financial barriers of sequencing for improved diagnosis and monitoring of disease progression.