Researchers have provided a proof in principle that it may be feasible to detect cancer with whole-genome sequencing technology applied to cell-free DNA found in plasma samples.

Researchers at Johns Hopkins University have provided a proof in principle that it may be feasible to detect cancer with whole-genome sequencing technology applied to cell-free DNA found in blood samples.

The scientists took blood samples from 10 healthy people and 10 patients who had late-stage colorectal or breast cancer and sequenced circulating cell-free DNA in the blood (Sci Transl Med 2012;162:162ra154). The researchers identified structural rearrangements or copy number changes in the blood DNA of all of the cancer patients; they did not find these changes in blood DNA from healthy subjects.

“This approach is highly specific for detecting cancer,” says Victor Velculescu, MD, PhD, a coauthor of the study and professor of oncology and codirector of the Cancer Biology Program at Johns Hopkins in Baltimore, MD. He says that existing blood tests for cancer depend on protein levels that can rise and fall based on events other than tumor growth, whereas the DNA changes that he and his colleagues found exist only in cancer cells. Velculescu also points out that there are many types of cancer for which researchers have yet to find a validated circulating protein marker.

Previous studies required samples of the original tumor and knowledge of the mutations in that tumor to find the same changes in blood DNA. The new technique eliminates the need for original tumor samples; in fact, the scientists found changes that could potentially guide anticancer drug choices. They identified amplification of 2 known oncogenes, including ERBB2, which is targeted by trastuzumab (Herceptin; Genentech), in a colon cancer patient.

Velculescu says larger clinical trials will be needed to determine the best applications of this approach. The team has started looking at patients with early-stage tumors to see how useful the technique will be in that setting. They believe this effort may be more challenging than it has been with advanced tumors because a smaller amount of circulating DNA may be produced by cancers at an early stage. The researchers are also working with tumor types other than breast and colorectal and have found chromosomal changes in circulating DNA in every type of cancer they've looked at so far.

For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.

©2012 American Association for Cancer Research.
2012