Ultra-Deep Sequencing Data From A Liquid Biopsy Proficiency Study Demonstrating Analytic Validity

By Binsheng Gong, Ira W. Deveson, Timothy Mercer, Donald J. Johann Jr, Wendell Jones, Weida Tong, and Joshua Xu

Precision oncology utilizes next generation sequencing (NGS) of tumors for the detection of mutations that cause cancer. This can lead to more specific and individualized treatments. NGS can also be used to detect DNA shed by a tumor into the blood (aka liquid biopsy (LBx)). Our corresponding proficiency study addresses the accuracy and reproducibility of ctDNA assays using a unique set of reference materials, associated analytical frameworks, and suggested best practices. The data and methods from this study represent a seminal piece of infrastructure for future validation of liquid biopsy methods and tools.

Liquid biopsy science and clinical applications are progressing rapidly. The first liquid biopsy assay approved by the FDA in 2016 was PCR-based¹ . Four years later there were two FDA approvals for liquid biopsy tests that were NGS-based^2,3. It is important to recognize the advantages of liquid biopsy assays versus traditional solid tumor approaches. These advantages include: i) increased safety since only a routine blood draw is required; ii) faster assay turn-around time since there is no need to schedule and coordinate a small operation or image-guided invasive procedure; iii) the potential ability to assess the heterogeneity of the malignant process, meaning assessing DNA from both the primary tumor and metastatic foci; iv) longitudinal testing prospects with time-based analyses that have not been possible before primarily due to patient safety issues; and v) new treatment monitoring strategies. For instance, blood is collected at a patient’s home for ctDNA analysis, then a medical oncologist can adjust the therapeutic plan. This can all happen outside of a traditional hospital or medical office environment.