Deep Sequencing of Circulating Tumor DNA Detects Cancers Early

However, this approach has generally been applied for the monitoring of patients with existing tumors. It has not been useful for early diagnosis of cancer because of insufficient sensitivity to detect very small tumors that only shed minute quantities of DNA into the blood, as well as difficulties with identifying cancer-associated genetic changes without knowing what mutations are present in the primary tumor.

To address these limitations, investigators at Johns Hopkins University (Baltimore, MD, USA) developed the TEC-Seq approach, which allowed ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. The TEC-Seq deep sequencing method, which reads the DNA base code 30,000 times, was used to screen patients' blood samples for mutations within 58 genes widely linked to various cancers.

Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Genomic sequencing of tumors removed from 100 of the 200 patients revealed that 82 had mutations in their tumors that correlated with the genetic alterations found in the blood.

"The challenge was to develop a blood test that could predict the probable presence of cancer without knowing the genetic mutations present in a person's tumor," said senior author Dr. Victor Velculescu, professor of oncology at Johns Hopkins University. "This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high accuracy sequencing method is a promising approach to achieve this goal."

The TEC-Seq study was published in the August 16, 2017, online edition of the journal Science Translational Medicine.

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