# Genome-wide cell-free DNA fragmentation in patients with cancer

Source: https://onco.cc/key-papers/paper-cristiano-delfi-fragmentomes-nature-2019/  
OnCo record `paper-cristiano-delfi-fragmentomes-nature-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The DELFI paper showed that the size and spacing of DNA fragments in blood differ in people with cancer, enough to detect seven cancer types in a laboratory comparison.

## Summary

Cristiano and colleagues developed DELFI, which reads genome-wide fragmentation profiles of cell-free DNA from low-coverage whole-genome sequencing. In 236 patients with breast, colorectal, lung, ovarian, pancreatic, gastric or bile duct cancer and 245 healthy individuals, a machine-learning model detected cancer with sensitivities of 57% to more than 99% across the seven types at 98% specificity and localised tissue of origin to a limited number of sites in 75% of cases. Combined with mutation analysis, the approach detected 91% of patients with cancer.

## Fields

- Kind: Key paper
- Last checked: 2026-10-29
- Journal: Nature
- Year: 2019
- DOI: 10.1038/s41586-019-1272-6
- Authors: Cristiano S, Leal A, Phallen J, et al.
- Findings: Sensitivity 57% to more than 99% across seven cancer types at 98% specificity.; Tissue of origin narrowed to a few sites in 75% of cases.; With mutation analysis, 91% of patients with cancer detected.
- What it means: Fragment patterns are a cheap signal that needs only shallow sequencing; Delfi Diagnostics now sells a lung-only test built on it, and several multi-cancer tests add fragmentomics to methylation.
- Caveats: Case-control with known cancers; not a screening result.

## Sources

- Nature 2019: DELFI: https://doi.org/10.1038/s41586-019-1272-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31142840/

## Connected records

- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [cfDNA fragmentomics](https://onco.cc/technologies/fragmentomics/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- companies: [DELFI Diagnostics](https://onco.cc/companies/delfi-diagnostics/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/)
- journals: [Nature](https://onco.cc/journals/nature/)

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