Scalable Whole-exome Sequencing of Cell-free DNA Reveals High Concordance with Metastatic Tumors

We performed whole genome sequencing (WGS) of cell-free DNA (cfDNA) from patients with metastatic cancer, and in a subset we performed whole-exome sequencing (WES) from cfDNA and matched tumor biopsies with germline DNA, and in another subset performed targeted panel sequencing from cfDNA with matched germline. Using ichorCNA, a software tool that quantifies tumor content in ultra-low pass WGS (~0.1x) of cfDNA without prior genomic characterization of the tumor, we show genome-wide concordance between cfDNA and tumor biopsies and detectability of high tumor fractions (>0.1) in the cfDNA of many patients with metastatic cancer. We then established that WES of cfDNA can enable comprehensive profiling of tumors from blood, with high tumor-content cfDNA samples demonstrating concordance of... (for more see dbGaP study page.)