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Nowhere to hide: Blood-based cancer monitoring gets ever more sensitive

Diehn and Alizadeh

A quick update on a fascinating advance in cancer detection that I've written about before, which is the increasing ability of researchers to detect the presence of DNA fragments from cancer cells in an easily obtained blood sample. Researchers in the Stanford laboratories of radiation oncologist Maximilian Diehn, MD, PhD, and hematologist and oncologist Ash Alizadeh, MD, PhD, have now come up with a significantly improved way to discern the presence of the cancer's genetic material.

They focused their study on non-small-cell lung cancer, but the technique should be applicable to many other cancers and other health-care needs. They published their results today in Nature Biotechnology.

As Diehn explained in our release:

Now we can detect even more sensitively the presence of specific mutations in the cancer DNA that could help drive treatment choices or detect the presence of residual cancer. We’re getting closer to greatly reducing the need for invasive biopsies to identify tumor mutations or track response to therapies.

The advance builds upon Alizadeh and Diehn's previous work, which was published in Nature Medicine in 2014. In that article, they described a technique called CAPP-Seq that captures circulating tumor DNA from a patient's blood. In the current work, they describe a new, two-pronged approach, called “integrated digital error suppression,” or iDES, that can improve the sensitive of CAPP-Seq by about 15 times.

iDES combines a genetic bar-coding technique to tag DNA in the blood with a data-polishing step that pinpoints and eliminates many common sequencing errors that can mask the presence of cancer-associated mutations.

As Alizadeh explained:

Our technique is a significant advance over prior bar-coding methods because it eliminates more false positives without sacrificing true positives. By tagging DNA molecules at the top of the food chain, so to speak, we can keep track of which molecules have been faithfully reproduced during the sequencing process and which have accumulated errors that were not present in a patient’s tumor or bloodstream.

More research is necessary to conclusively determine whether the technique truly improves cancer patient outcomes or reduce health care costs, but I'm going to be watching this closely. Eliminating or reducing invasive biopsies while facilitating ongoing monitoring of a tumor's response to therapy or the evolution of mutations is an exciting prospect.

Previously: Blood will tell: In Stanford study, tiny bits of circulating tumor DNA betray hidden cancers, Researchers develop molecular target for brain cancer and Linking cancer gene expression with survival rates, Stanford researchers bring "big data" into the clinic
Photo of Maximilian Diehn (left) and Ash Alizadeh by Mark Tuschman

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