Combining Liquid Biopsy Techniques Improves Cancer Detection

The study covered in this summary was published on as a preprint and has not yet been peer reviewed.

Key Takeaway

  • Combining several cell-free DNA (cfDNA) liquid biopsy techniques improves cancer surveillance and detection in patients with Li-Fraumeni syndrome (LFS) and likely other hereditary cancer syndromes.

Why This Matters

  • People with LFS have nearly a 100% lifetime risk of developing a wide range of cancers.

  • Patients routinely undergo intensive surveillance, which significantly improves survival but is also burdensome to patients and providers.

  • Liquid biopsy, analyzing cfDNA in blood plasma, is gaining traction for early cancer detection. 

  • Many cfDNA studies, however, focus on using only one technique at a time.

  • The new investigation suggests that a combination of approaches is better at detecting cancer signals in LFS, laying the groundwork for improved and less burdensome surveillance in patients with hereditary cancer syndromes.

Study Design

  • The team applied three cfDNA techniques — shallow whole genome sequencing, targeted panel sequencing, and cell-free methylated DNA immunoprecipitation sequencing — to 196 blood samples from 89 patients with LFS, including 26 children.

  • Overall, 27 patients had active cancer at the time of blood draw; 62 were cancer negative.

Key Results

  • An integrated analysis detected cancer-associated signals in 79.4% of samples from patients with active cancer, a substantial improvement over results from each technique individually. 

  • Signals were detected in 17.6% of cancer-negative patients who were later diagnosed with tumors by conventional means, in one case 16 months beforehand.

  • The team also identified a set of LFS-specific methylation sites, which could be used to diagnose LFS in patients without a detectable germline TP53 mutation as well as stratify families with LFS-like phenotypes for increased surveillance.


  • No study limitations were reported.


  • The work was funded by the Terry Fox Research Institute and the Canadian Institutes for Health Research.

  • The senior investigator has reported receiving personal fees from AstraZeneca, Chrysalis Biomedical Advisors, Illumina, Merck, and PACT Pharma, and grants from Roche/Genentech.

This is a summary of a preprint research study, Integrated analysis of cell-free DNA for the early detection of cancer in people with Li-Fraumeni Syndrome, led by Derek Wong of Princess Margaret Cancer Centre, Toronto, Ontario, Canada, provided to you by Medscape. The study has not been peer reviewed. The full text can be found at

M. Alexander Otto is a physician assistant with a master s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is also an MIT Knight Science Journalism fellow. Email: [email protected]

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