DNA-based blood test finds early cancer like a 'needle in a haystack'

By John Murphy, MDLinx
Published August 17, 2017

Key Takeaways

Cancer researchers have developed a blood test that detects tiny cancer-specific DNA alterations to identify 59% to 71% of patients with early-stage colorectal, ovarian, lung, and breast cancer.

The results, published in Science Translational Medicine, indicate that the test could find many early tumors, highlighting its potential use for early cancer detection and early intervention.

Creating a reliable and noninvasive method for detecting early-stage tumors has been a challenge for cancer researchers. For this study, investigators developed a genomic sequencing method called targeted error correction sequencing (TEC-Seq), which allows ultrasensitive evaluation of changes in DNA sequences specific to tumors.

“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,” said corresponding author Victor E. Velculescu, MD, PhD, Co-Director of Cancer Biology and Professor of Oncology and Pathology, Johns Hopkins Kimmel Cancer Center, Baltimore, MD.

The sequencing method is based on targeted capture of multiple regions of the genome and “deep sequencing,” which reads each DNA fragment about 30,000 times.

“We’re trying to find the needle in the haystack, so when we do find a DNA alteration, we want to make sure it is what we think it is,” Dr. Velculescu said.

Until now, approaches using next-generation sequencing and advanced computational methods for detecting DNA mutations have been applied primarily in patients with late-stage cancers, or have used tumor tissue sequencing to guide mutational analyses in the blood.

The goal for these researchers was to develop a cancer screening test that could pinpoint DNA alterations in the blood of seemingly healthy individuals.

“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,” Dr. Velculescu said.

In this study, the investigators used TEC-Seq to examine plasma samples from 194 patients who had been diagnosed with stage I or II cancer but had not been treated, as well as 44 individuals with no known cancer. The researchers analyzed the samples against 58 cancer-related genes comprising 80,930 captured bases.

Of the 194 patients analyzed, more than three quarters (71%) of patients with colorectal cancer, two-thirds (68%) of patients with ovarian cancer, and most of the patients with lung (59%) and breast cancer (59%) had detectable mutations.

In all, the investigators detected cancer-derived mutations in 62% of patients with stage I and II cancers and in 77% of patients with stage III and IV cancers.

Next, the researchers analyzed tumor biopsies from the cancer patients and determined that 82% correlated with the DNA mutations found in their blood samples—a “high concordance.”

No tumor-derived mutations were found in the blood samples of the 44 healthy individuals.

“The survival difference between late- and early-stage disease in these cancers accounts for more than a million lives worldwide each year,” the authors wrote in their paper. “These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.”

The investigators acknowledged that this screening method will first require larger validation studies before it can be implemented on a broad scale.

Share with emailShare to FacebookShare to LinkedInShare to Twitter