Accurate Estimation Of Circulating Tumor Dna Fraction From Ultra Low-Pass Whole-Genome Sequencing

Early detection of recurrence is critical to improve the survival of cancer patients. Blood-based “liquid biopsies” provide a minimally invasive method to detect variants, and ultra low-pass whole-genome sequencing (LPWGS) can accurately and sensitively detect low fractions of circulating tumor DNA in blood plasma. We previously conducted LPWGS on approximately 400 samples (primarily from lung, breast, prostate, and pancreatic cancers) residual to samples previously analyzed with our xF liquid biopsy assay. In this analysis, we demonstrate that circulating tumor fraction estimates from LPWGS correlate with the maximum detectable pathogenic variant allele fraction, and where there are discrepancies the LPWGS estimates are more reasonable. We also show differences in tumor fractions and ploidy between cancer cohorts and stages. Our results suggest LPWGS provides an accurate measure of the fraction of circulating DNA derived from tumors across cancer cohorts and stages. Citation Format: Justin Finkle, Christine Lo, Hala Boulos, Terri Driessen, Wei Zhu, Robert Tell. Accurate estimation of circulating tumor DNA fraction from ultra low-pass whole-genome sequencing [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3106.