DNA Sequencing of Liquid Biopsy Specimens Increases Accuracy of Prostate Cancer Diagnosis

Next-generation sequencing analysis of DNA in the serum, a technique called liquid biopsy, can distinguish between prostate cancer patients, normal individuals, patients with benign hyperplasia, and those with noncancerous prostatitis.

Genomic instability resulting in copy number variation is characteristic of malignant transformation and may be identified through next-generation massive parallel sequencing. Tumor-specific cell free DNA (cfDNA) is released by dying cancer cells into the serum and plasma where it provides a real time, easily accessible target for this approach.


Investigators at Vanderbilt University (Nashville, TN USA) extracted DNA from serum of 204 patients with prostate cancer, 207 male controls, 10 patients with benign hyperplasia, and 10 with prostatitis. DNA was amplified by use of random primers, tagged with molecular identifiers, sequenced on a Life Technologies (Carlsbad, CA, USA) SOLID system, and aligned to the human genome.

Assessment of the results allowed the investigators to establish a model that discriminated prostate cancer from controls with an AUC (area under the curve) of 0.92 (0.87–0.95), reaching a diagnostic accuracy of 83%. Both benign prostatic hypertrophy and prostatitis could be distinguished from prostate cancer by use of cfDNA, with an accuracy of 90%.

"Based on the reported data and work in progress, I believe the "liquid biopsy" will revolutionize cancer diagnostics, not only before a patient begins therapy but also following patient responses to therapy," said contributing author Dr. William Mitchell, professor of pathology, microbiology, and immunology at Vanderbilt University. "Since cell-free DNA has a relatively short half-life in the circulation, sequencing of cell-free DNA soon after therapy may be used to detect minimal residual disease in solid tumors."

The study was published in the January 2015 issue of the journal Clinical Chemistry.

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