Journal: EMBO molecular medicine
This study introduces informCNA, a bioinformatics approach to improve detection of circulating tumor DNA (ctDNA) using shallow whole-genome sequencing (sWGS) of cell-free DNA.
Key points:
- Problem: Conventional ctDNA detection via copy number aberration (CNA) analysis on sWGS typically detects tumor fractions only down to ~3%, limiting utility for early relapse detection and minimal residual disease monitoring.
- Approach:
- • informCNA uses CNA profiles derived from either tumor tissue or high–tumor-fraction pre-treatment plasma as a personalized reference.
- • It then applies this individualized CNA “fingerprint” to interpret subsequent low-depth plasma sWGS data, increasing sensitivity for low-level ctDNA.
- Performance:
- • Achieves ctDNA detection at tumor fractions as low as 0.2% across multiple cancer types (based on the data presented).
- Clinical application in ovarian cancer:
- • Evaluated in 177 serial plasma samples from 18 patients.
- • ctDNA dynamics measured by informCNA were highly concordant with CA-125 trends.
- • informCNA identified recurrence a median of 3.7 months earlier than CA-125.
- Implications for practice:
- • Demonstrates that personalized CNA-based analysis of sWGS can be a sensitive, minimally invasive, and relatively cost-effective strategy for monitoring disease burden and detecting relapse earlier than standard serum markers in ovarian cancer, with potential applicability across tumor types.