EMBO Mol Med. 2026 Mar 19.
Ze Zhou,
Ros Cutts,
Sarah Hrebien,
Christina X Zhang,
Isaac Garcia-Murillas,
Woody Z Zhang,
Alexander M Frankell,
Wendy N Cooper,
Amit Roshan,
Nicholas C Turner,
Tommy Kaplan,
Nitzan Rosenfeld,
Hui Zhao.
Methods to detect circulating tumor DNA (ctDNA) enable minimally invasive responsive monitoring of cancer dynamics. However, sensitive and cost-effective methods are still lacking. Current methods for detecting cancer signals in shallow whole-genome sequencing (sWGS) data from cell-free DNA (cfDNA) via copy number aberration (CNA) analysis typically have a limit of detection of approximately 3% tumor fraction (TF). We developed informCNA, a bioinformatics method that leverages CNA information from sWGS of tumor or pre-treatment plasma samples with high TF as references, enabling ctDNA detection down to 0.2% TF across multiple cancer types. In 177 serial plasma samples from 18 patients with ovarian cancer, informCNA showed high concordance with the standard serum protein marker CA-125 and identified recurrence a median of 3.7 months earlier than CA-125 test. These results demonstrate the potential of personalized CNA analysis through sWGS for estimating ctDNA burden, enabling precise and cost-effective disease monitoring and early detection of relapse.
Keywords: Copy Number Aberration (CNA); Liquid Biopsy; Tumor-informed; cfDNA; ctDNA