A new blood test uses next-generation sequencing technology to probe DNA for tiny chemical tags (methylation) that influence whether genes are active or inactive. When applied to nearly 3,600 blood samples — some from patients with cancer and some from people who had not been diagnosed with cancer at the time of the blood draw — the test successfully picked up a cancer signal from the cancer patient samples and correctly identified the tissue from where the cancer began (the tissue of origin). The test’s specificity — its ability to return a positive result only when cancer is actually present — was high, as was its ability to pinpoint the organ or tissue of origin.
The new test looks for DNA, which cancer cells shed into the bloodstream when they die. In contrast to “liquid biopsies,” which detect genetic mutations or other cancer-related alterations in DNA, the technology focuses on modifications to DNA known as methyl groups. Methyl groups are chemical units that can be attached to DNA in a process called methylation, to control which genes are “on” and which are “off.” Abnormal patterns of methylation turn out to be, in many cases, more indicative of cancer — and cancer type — than mutations are. The new test zeroes in on portions of the genome where abnormal methylation patterns are found in cancer cells.
Researchers analyzed cell-free DNA (DNA that had once been confined to cells but had entered the bloodstream upon the cells’ death) in 3,583 blood samples including 1,530 from patients diagnosed with cancer and 2,053 from people without cancer. The patient samples comprised more than 20 types of cancer including hormone receptor-negative breast, colorectal, esophageal, gallbladder, gastric, head and neck, lung, lymphoid leukemia, multiple myeloma, ovarian, and pancreatic cancer.
The overall specificity was 99.4%, meaning only 0.6% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for detecting a pre-specified, high-mortality cancer (the percent of blood samples from these patients that tested positive for cancer) was 76%. For the 97% of samples that returned a tissue of origin result, the test correctly identified the organ or tissue of origin in 89% of cases.
Detecting even a modest percent of common cancers early could translate into many patients who may be able to receive more effective treatment if the test were in wide use.