Scientists have developed a blood test that spots tiny amounts of cancer-specific DNA, a step towards accurate screening of seemingly healthy patients for early stage cancers.
The noninvasive test correctly identified more than half of 138 people with relatively early stage colorectal, breast, lung and ovarian cancers, say researchers at Johns Hopkins University.
The test, they say, is a step forward in that it can distinguish between DNA shed from tumors and other altered DNA in the blood that might otherwise be mistaken for cancer biomarkers.
“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, professor of oncology at the Johns Hopkins Kimmel Cancer Center.
The research, performed on blood and tumor tissue samples from 200 people with all stages of cancer in the United States, Denmark, and the Netherlands, appears in the journal Science Translational Medicine.
Velculescu says populations that could benefit most from early blood-based detection include those at high risk for cancer. That includes tobacco smokers, for whom standard CT scans for lung cancer often lead to false positives. Another at-risk population that could benefit is women with inherited BRCA1 and BRCA2 mutations for breast and ovarian cancer.
To develop a test that could be used to screen for early cancers in seemingly healthy people, scientists had to learn to spot previously unidentified DNA alterations lurking in a person’s blood.
“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,” Velculescu says.
The goal, adds Jillian Phallen, a graduate student involved in the research, was to develop a test accurate enough to detect cancer when present, but with reduced risk of “false positives” that can lead to unnecessary treatment.
To develop their new test, Velculescu, Phallen, and their colleagues obtained blood samples from cancer patients and screened for mutations within 58 genes widely linked to various cancers.
Overall, the scientists were able to detect 62 percent of stage I and II cancers; specific results varied between 45 percent and 89 percent depending on which of the two stages and which type of cancer.
For stage III and IV cancers, successful detections ranged from 46 to 93 percent, depending on stage and cancer type. There were no false positives.
The blood test is promising but needs to be validated in studies of much larger numbers of people, the scientists say.
Other scientists who contributed to the research are from Johns Hopkins; the University of California, San Diego; Personal Genome Diagnostics Inc.; Aarhus University Hospital, Herning Regional Hospital and Hvidovre Hospital in Denmark; and the University of Amsterdam, VU University Medical Center; and the Netherlands Cancer Institute in the Netherlands.
Funding came from the National Cancer Institute, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Stand Up to Cancer-Dutch Cancer Society International Translational Cancer Research Dream Team Grant, the Commonwealth Foundation, the Cigarette Restitution Fund Program, the Burroughs Wellcome Fund, the Maryland-Genetics, Epidemiology and Medicine Training Program, the International Association for the Study of Lung Cancer/Prevent Cancer Foundation, the Danish Council for Independent Research, the Danish Council for Strategic Research, the Novo Nordisk Foundation, and the Danish Cancer Society.
Phallen and Velculescu are among the team members who are inventors named in patent applications related to this research. Velculescu, a founder of Personal Genome Diagnostics and a member of its scientific advisory board and board of directors, also owns stock in the company, subject to restrictions under Johns Hopkins policy. Velculescu is also on the scientific advisory board for Ignyta. The arrangements are managed by Johns Hopkins in accordance with its conflict of interest policies.