Tracking tiny amounts of a patient’s unique cancer DNA could provide a new way of detecting small tumors or stray cancer cells that linger after treatment. Researchers from Johns Hopkins University and Life Technologies Corporation, a biotechnology tools company, used fast and cheap sequencing methods to spot genetic alterations in breast and bowel cancers in individual patients. Once found, the researchers used stretches of rearranged DNA to construct personalized biomarkers that allow them to detect even faint traces of tumor DNA.
As our understanding of cancer grows, scientists are beginning to view it as a chronic disease that is very difficult to eliminate entirely. Technologies like this one could provide ways to track it and keep it in check. The technique exploits a well-known tendency of tumors to sport scrambled chromosomes. Such swapping around of big chunks of DNA may in fact be one of the key events contributing to cells becoming cancerous in the first place.
Existing biomarkers are mostly protein-based and available for only some types of cancers. An example is the PSA protein that indicates prostate cancer. But because these proteins aren’t always unique to cancer cells, they aren’t very sensitive. “Our genetic markers work because they are extremely different” from the DNA in healthy cells, says Victor Velculescu, who led the research. “We could easily find one piece of cancer DNA among 400,000 normal ones.” The research was published today in the journal Science Translational Medicine.
While scientists have long known that cancer cells tend to harbor scrambled DNA, using this information to track the progression of cancer, or the effectiveness of treatment, has been a challenge. That’s because the precise nature of the genetic change is different in each patient, making these markers hard to find. The notable exceptions are several types of blood cancers that always display the same type of DNA rearrangement.
To tackle solid tumors with unpredictable genetic changes, Velculescu’s team turned to new sequencing technologies that have brought sequencing costs down tremendously over the past few years. Cheap sequencing meant the scientists could search the entire genome for signs of cancer. They used technology from Applied Biosystems, part of Life Technologies, to sequence the genomes of four bowel and two breast cancer genomes along with the genomes of four patients’ healthy tissue.