August 08, 2019
3 min read

Cell-free DNA may aid in early detection, monitoring of various cancer types

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Victor E. Velculescu
Victor E. Velculescu

Cell-free DNA fragmentation profiles could be used for screening, early detection and monitoring of certain cancer types, study findings suggest.

Cell-free DNA in the blood provides a noninvasive diagnostic avenue for patients with cancer. However, characteristics of the origins and molecular features of cell-free DNA are poorly understood,” Victor E. Velculescu, MD, PhD, professor of oncology and co-director of the cancer biology program at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and colleagues wrote.

Investigators developed an approach to evaluate fragmentation patterns of cell-free DNA across the genome. They used a blood-based assay to assess the fragmentation profiles of 208 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer. They analysis also included a comparison cohort with 215 healthy controls.

Results showed profiles of healthy controls reflected nucleosomal patterns of white blood cells, whereas altered fragmentation profiles were observed among those with cancer.

“Fragmentation profiles could be used to identify the tissue of origin of the cancers to a limited number of sites in 75% of cases,” Velculescu and colleagues wrote. “Combining our approach with mutation-based cell-free DNA analyses detected 91% of patients with cancer.”

HemOnc Today spoke with Velculescu about the study, the potential implications of the findings, and the direction he believes subsequent research should take.

Question: What prompted this research?

Answer : We need to improve the way we detect cancer. Existing methods of early detection are useful. These include colonoscopies and CT screening for lung cancer. However, compliance with these approaches is not as high as it could be. In some cases — for example, with lung cancer — there may be many false positives with CT scans. We need to make these early detection approaches better from a performance perspective, but also easier to perform in the real-world setting, and to have a higher fraction of patients undergo such tests. We had been thinking for a long time about a blood-based test and had been frustrated by the existing approaches — some of which we have developed for looking at conventional markers in the blood, such as mutations or methylation. We realized we had to do something totally different to increase the characteristics and performance of these tests.


Q: How did you conduct the study?

A: The research evaluated blood samples from 208 patients with various stages of breast, colorectal, lung, ovarian, pancreatic and gastric or bile duct cancer from various countries around the world. We also obtained blood samples from 215 healthy individuals. We identified DNA from the blood samples and analyzed the DNA using the novel approach. We then used a type of artificial intelligence to identify the abnormal patterns of DNA fragments in the blood of patients with cancer.

Q: What did you find ?

A: Anywhere from 57% to more than 99% of cancers could be detected — and we could also tell where the cancer was coming from. We identified the origin of the cancer in up to 75% of cases. This is very important because we need to both sensitively detect the cancer in the early stages and determine where the cancer is coming from, so that we know what to do next.

Q: What are the clinical implications of the findings?

A: This approach has potential for early detection of a variety of cancer types. These abnormal fragmentation patterns occur because of the way DNA is packaged inside cancer cells. With cancer cells undergoing replication and mitosis abnormally, this DNA packaging is never completed appropriately as would normally be the case for different cells in our bodies. Because of this, we could detect these different fragmentation patterns. The hope is that, in the long run, this kind of test will be available as a yearly test to detect whether an individual has a cancer signal and where that early cancer may be coming from. Ultimately, such an individual will be connected to the right specialist to potentially remove or treat that small lesion in a very specific way.

Q: Do you plan to conduct additional research on this?

A: Further research will be necessary to validate and extend these findings. However, because the test is so easy to administer and employs simple and inexpensive lab methods, we think that ultimately it will be more cost-effective than other tests, including other liquid biopsy analyses. – by Jennifer Southall


Cristiano S, et al. Nature. 2019;doi:10.1038/s41586-019-1272-6.

For more information:

Victor Velculescu, MD, PhD, can be reached at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, The Koch Cancer Research Building, 1550 Orleans St., Room 541, Baltimore, MD 21287; email:

Disclosure: Velculescu reports serving on the scientific advisory boards and boards of directors for Delfi Diagnostics and Personal Genome Diagnostics; stock ownership in Delfi Diagnostics and Personal Genome Diagnostics; and advisory roles with Daiichi Sankyo, Ignyta, Janssen Diagnostics and Takeda Pharmaceuticals.