In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer–specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early–stage colorectal, breast, lung and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumors and other altered DNA that can be mistaken for cancer biomarkers.

A report on the research, performed on blood and tumor tissue samples from 200 people with all stages of cancer in the U.S., Denmark and the Netherlands, appeared in the Aug. 16 issue of the journal Science Translational Medicine.

“This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high accuracy sequencing method is a promising approach to achieve this goal,” says Victor Velculescu, MD, PhD, professor of oncology at the Johns Hopkins Kimmel Cancer Center.

To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person’s blood but had not been previously identified.

“The challenge was to develop a blood test that could predict the probable presence of cancer without knowing the genetic mutations present in a person’s tumor,” says Velculescu.

The goal, adds Jillian Phallen, a graduate student at the Johns Hopkins Kimmel Cancer Center who was involved in the research, was to develop a screening test that is highly specific for cancer and accurate enough to detect the cancer when present, while reducing the risk of “false positive” results that often lead to unnecessary overtesting and overtreatments.

The task is notably complicated, says Phallen, by the need to sort between true cancer–derived mutations and genetic alterations that occur in blood cells and as part of normal, inherited variations in DNA.

As blood cells divide, for example, Velculescu says there is a chance these cells will acquire mistakes or mutations. In a small fraction of people, these changes will spur a blood cell to multiply faster than its neighboring cells, potentially leading to pre–leukemic conditions. However, most of the time, the blood–derived mutations are not cancer–initiating.

His team also ruled out so–called “germline” mutations. While germline mutations are indeed alterations in DNA, they occur as a result of normal variations between individuals, and are not usually linked to particular cancers.

To develop the new test, Velculescu, Phallen and their colleagues obtained blood samples from 200 patients with breast, lung, ovarian and colorectal cancer. The scientists’ blood test screened the patients’ blood samples for mutations within 58 genes widely linked to various cancers.