Tumour-Informed Copy Number Analysis Detects ctDNA Down to 0.2% Tumour Fraction
Researchers developed informCNA, a bioinformatics method that uses copy number aberration profiles from tumour or high-TF plasma samples to detect ctDNA in shallow whole-genome sequencing data at tumour fractions as low as 0.2% · far below the typical 3% threshold. In 177 serial samples from 18 ovarian cancer patients, the method showed high concordance with CA-125 and identified recurrence a median of 3.7 months earlier than the standard protein marker.
The original study
ctDNA monitoring using tumor-informed copy number analysis.
- Authors
- Zhou Z, Cutts R, Hrebien S, Zhang CX, Garcia-Murillas I, Zhang WZ, et al.
- Journal
- EMBO molecular medicine
- PMID
- 41857451
Original abstract
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.