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Toward a liquid biopsy

A team of scientists led by Maximilian Diehn and Ash Alizadeh of the Ludwig Center at Stanford has significantly boosted the sensitivity of a method to identify and sequence DNA shed into the blood by dead tumor cells. Such “liquid biopsies” could one day be a minimally invasive alternative to surgical biopsies of tumors.

The new approach, named integrated Digital Error Suppression (iDES), is reported in the March 28 issue of Nature Biotechnology. It detects errors that occur when circulating tumor DNA is captured and prepared for sequencing, and computationally removes such errors from the results. This permits researchers to more accurately identify true cancer-associated mutations from even very small amounts of starting material. iDES, the researchers report, can detect as few as one or two tumor DNA sequences among as many as 400,000 non-tumor DNA fragments in the blood. The original method, CAPP-Seq was also developed by Ludwig Stanford’s Diehn and Alizadeh.

Initially described in Nature Medicine in 2014, CAPP-Seq detects one tumor DNA fragment out of 5,000 ordinary DNA molecules floating in the blood. “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,” said Diehn, who like Alizadeh is also an assistant professor at the Stanford University School of Medicine. “We’re getting closer to greatly reducing the need for invasive biopsies to identify tumor mutations or track response to therapies.”

A more detailed article on the study is available here.


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