Tumor-Informed vs. Tumor-Agnostic ctDNA MRD Testing
ctDNA-based MRD assays differ fundamentally in their test design, sensitivity, and data handling. Understanding these differences is critical when selecting an approach for ultra-sensitive MRD monitoring in clinical practice and research.
Tumor-informed MRD testing
Tumor-informed MRD assays are designed based on patient-specific tumor mutations identified from tumor tissue. These variants are then used as personalized markers for longitudinal ctDNA monitoring in blood samples.
Tumor-agnostic ctDNA testing
Tumor-agnostic ctDNA assays analyze predefined genomic regions or mutation panels without prior knowledge of the individual tumor genome. These approaches can be applied without tumor tissue and are commonly used for mutation profiling or broader screening purposes.
Sensitivity and methodological considerations
Ultra-sensitive MRD detection requires the reliable identification of very low ctDNA levels against a high background of normal DNA. Tumor-informed assays leverage patient-specific variants, which reduces background noise and supports highly specific detection.
Tumor-agnostic approaches rely on recurrent mutations and may be limited by biological background signals such as clonal hematopoiesis, particularly at very low ctDNA levels.
Whole-genome sequencing and assay design
The breadth of genomic information used during assay design directly influences the selection of tumor-specific variants. Whole-genome sequencing enables comprehensive variant discovery across the entire tumor genome, supporting robust personalized assay design for MRD monitoring.
Approaches based on smaller genomic regions or predefined panels focus on a limited subset of variants and serve different clinical purposes.
Methodological comparison at a glance
Methodological comparison
| Dimension | Tumor-informed MRD | Tumor-agnostic ctDNA |
|---|---|---|
| Tumor tissue required | Yes | No |
| Test personalization | Patient-specific | Panel-based |
| Typical use case | Ultra-sensitive MRD monitoring | Mutation profiling / screening |
| Background noise | Low | Higher (e.g. clonal hematopoiesis) |
| Sensitivity at very low ctDNA | High | Method-dependent |
| Variant selection | Tumor-specific | Predefined |
| Longitudinal monitoring | Optimized | Limited |
Test execution and data processing in Germany and Europe
HPH MRD testing is performed entirely in Germany. Sample processing, sequencing, data analysis, and data storage take place locally and remain within Germany and the European Union. No transfer of patient samples or genomic data to the United States is required.
This approach supports compliance with European data protection requirements and provides clarity for clinical studies and healthcare institutions with strict data governance policies.
Clinical evidence
Multiple clinical studies and reviews have demonstrated the value of tumor-informed ctDNA approaches for MRD detection in various cancer types. Key publications include the DYNAMIC trial and multiple studies by Tie et al. and others.
Learn more
Learn more about the HPH MRD approach for tumor-informed, whole-genome sequencing-based MRD testing.