New strategies may increase the sensitivity of cancer surveillance in blood samples

Whole-genome sequencing-based error correction methods for detecting cancer in blood samples may be more sensitive and accurate in monitoring post-treatment disease status in cancer patients compared to previous methods. According to a recent survey published by Cheng et al. Natural Method. The findings may represent key steps towards the goal of screening based on routine blood tests for early cancer detection.

background

Blood test-based fluid biopsy techniques designed for early cancer detection and monitoring patient cancer burden can have significant benefits for cancer treatment. However, sensitive and accurately identifying cancer mutation signatures from low concentrations of tumor DNA in blood samples has a major challenge.

Previous studies have shown that blood samples can provide an opportunity to reliably detect advanced melanoma and lung cancer, even without access to sequence data from tumor samples.

“We are now in an era of low-cost DNA sequencing. This study utilized that to apply whole-genome sequencing techniques that were previously considered very impractical,” explained the senior study author. Dan Landau, MD, PhDBibliowicz Family Medicine Professor, a member of the Institute of Precision Medicine, an oncologist at the New York Presbyterian/Weill Cornell Medical Center, and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, a member of the New York Genome Center.

Research methods and results

In this study, researchers benchmarked the cancer detection performance of a new commercial sequencing platform. They demonstrated that the low cost of sequencing platforms allows for depths of whole-genome sequencing coverage, which would have been very expensive in older technologies. Using that platform alone and using known mutation patterns in patient tumors as a guide, researchers were able to detect circulating tumor DNA in patient blood samples at concentrations ranging from 1 million copies. All samples included in this study were collected after informed consent was obtained from the patients.

The researchers then enhanced the accuracy of the approach with error correction methods that utilize redundant information with natural bidirectional DNA. The combined techniques had a low error rate, so in principle they can be used in blood samples without the need for patient tumor access.

Conclusion

The results of this study demonstrated the possibility of a novel, highly sensitive, low-error approach to detect very low cancer levels in urothelial carcinoma and melanoma patients from blood samples alone.

“This collaboration allowed us to analyze circulating tumor DNA from patients. [urothelial carcinoma] Identification… a clear mutation signature” emphasized by the co-established authors. Bishoy M. Faltas, MDChief Research Officer of the Institute of Precision Medicine, and Associate Professor of Medicine, Weil Cornell Medicine, a urological oncologist at the New York Presbyterian/Weil Cornell Medical Center. “Incorporating these signatures into the analysis significantly increased the sensitivity of circulating tumor DNA detection,” he added.

“For example, we were able to see an increase in circulating tumor DNA levels after treatment of advanced or recurrent cancer patients. Dr. Alexander ChenHigher Technical School and Research Center at the University of Montreal Hospital Centre.

“These results allow us to think about a future where cancer can be detected and tracked through blood tests alone,” concluded Dr. Landau.

Disclosure: The study was supported in part by the establishment of the National Institutes of Health, the Mark Foundation Aswire Award, the Medical Scientist Award of the Burrows Welcome Fund, and the Investigator Awards by the Melanoma Research Alliance. Visit us for full disclosure of research authors Nature.com.