Researchers developed a way to identify tumor cell DNA in blood samples taken from patients with different types of cancer.
The findings suggest a noninvasive way to detect the early stages of cancer and help guide cancer treatment.
Tumor cells release small pieces of DNA into the bloodstream. These pieces, called circulating tumor DNA, may help doctors detect tumors and track their progress.Jonathan Bailey, NHGRI
Cancer is caused by changes to genes that control the way our cells grow and divide. In all types of cancer, some of the body’s cells begin to divide without stopping and spread into surrounding tissues. Cancer can start almost anywhere among the trillions of cells in the human body.
Each cancer has a unique combination of genetic changes. As the cancer grows, it continues to change. Even within the same tumor, different cells may have different genetic changes. This is one reason that cancers become more difficult to treat with time. The ability to detect early genetic changes in cancer could help doctors save many lives.
Recent studies have shown that DNA from tumors can be detected in the blood. A team of scientists led by Dr. Victor Velculescu at the Johns Hopkins Kimmel Cancer Center investigated whether they could detect circulating DNA from early tumors. The study was funded in part by NIH’s National Cancer Institute (NCI). Results were published in the August 16, 2017, issue of Science Translational Medicine.
The team analyzed blood samples taken from 44 healthy people and 200 patients with different stages and types of cancer. They designed a DNA sequencing approach called targeted error correction sequencing. The method uses “deep sequencing,” which is an ultrasensitive approach to reading DNA. By scanning the DNA 30,000 times, the technique allows for highly accurate detection of any changes in the DNA sequence.
Using this method, the team screened the blood samples for mutations within 58 known cancer-related genes. They detected no tumor-derived mutations in the blood samples from the healthy people. However, in the samples from patients with colorectal, breast, lung, or ovarian cancer, the technique identified tumor-related DNA mutations in 48 of 62 patients (77%) with advanced cancer (stages III and IV) and in 86 of 138 patients (62%) with stage I or stage II cancer.
The team also looked at whether the amount of tumor DNA circulating in the blood before colorectal cancer surgery could help predict patient outcomes. Higher levels of tumor DNA in the blood before surgery was correlated with increased chances of the disease returning and with decreased chances of survival. This result suggests that the approach could help doctors better manage treatments.
“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,” Velculescu says.
These findings suggest that circulating tumor DNA might be used to help detect early cancers and guide the care of cancer patients. More studies are needed in a larger number of people to validate whether this approach will be helpful in the clinic.
References: Direct detection of early-stage cancers using circulating tumor DNA. Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, Anagnostou V, Fiksel J, Cristiano S, Papp E, Speir S, Reinert T, Orntoft MW, Woodward BD, Murphy D, Parpart-Li S, Riley D, Nesselbush M, Sengamalay N, Georgiadis A, Li QK, Madsen MR, Mortensen FV, Huiskens J, Punt C, van Grieken N, Fijneman R, Meijer G, Husain H, Scharpf RB, Diaz LA Jr, Jones S, Angiuoli S, Ørntoft T, Nielsen HJ, Andersen CL, Velculescu VE. Sci Transl Med. 2017 Aug 16;9(403). pii: eaan2415. doi: 10.1126/scitranslmed.aan2415. PMID: 28814544.
Funding: NIH’s National Cancer Institute (NCI); Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Stand Up to Cancer–Dutch Cancer Society; Commonwealth Foundation; Cigarette Restitution Fund; Burroughs Wellcome Fund; Maryland Genetics, Epidemiology and Medicine Training Program; International Association for the Study of Lung Cancer/Prevent Cancer Foundation; Danish Council for Independent Research; Danish Council for Strategic Research; Novo Nordisk Foundation; and Danish Cancer Society.
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