Glossary · Markers and tests
Liquid biopsy
In one sentence
A liquid biopsy is the analysis of tumour-derived material, mainly circulating tumour DNA (ctDNA), in a body fluid such as blood. It allows genetic changes in a cancer to be studied without a tissue biopsy.
Also known as: liquid biopsies · circulating tumour DNA · circulating tumor DNA · ctDNA · cfDNA · cell-free DNA
What is a liquid biopsy?
Cells, including cancer cells, release fragments of DNA into the bloodstream when they die. This cell-free DNA (cfDNA) was first described in human plasma in 1948 by Mandel and Métais. In someone with cancer, a fraction of that DNA comes from the tumour: this is circulating tumour DNA (ctDNA), which carries the same genetic changes as the tumour itself.
A liquid biopsy analyses that material, although the term also covers circulating tumour cells, extracellular vesicles and RNA. Its main advantage is that it needs only a blood sample, which can be repeated over time.
What it is used for
The ESMO Precision Medicine Working Group’s recommendations on ctDNA assays (Pascual et al., Annals of Oncology, 2022) summarise current practice:
- Advanced cancer: validated, adequately sensitive assays are useful for identifying actionable mutations to guide targeted therapy, provided their limitations are taken into account.
- Tissue still preferred: tissue testing remains the preferred option for many patients, because ctDNA assays are less good at detecting gene fusions and copy-number changes.
- Minimal residual disease and early detection: promising applications that are still being evaluated.
Limitations
- If a tumour sheds little DNA (small tumours, certain sites), ctDNA may go undetected: a negative result does not exclude cancer.
- With age, blood cells acquire mutations (clonal haematopoiesis) that can be mistaken for tumour changes.
- Sample handling and plasma processing affect the result; specific tubes and time limits are required.
The changes detected are genetic variants that need to be classified and interpreted using recognised databases and criteria.
Example
A patient with advanced lung cancer does not have enough tissue for molecular testing. The oncology team requests a liquid biopsy, which finds an EGFR mutation for which a targeted treatment exists. Months later, a further blood sample is used to look for resistance mutations. On both occasions, the clinical decision combines the result with imaging and the patient’s progress.
Liquid biopsy at Xenogene
VERUM is Xenogene’s oncology liquid biopsy test. According to its product page, it combines germline analysis of more than 100 hereditary cancer predisposition genes with circulating tumour DNA analysis by Nanopore sequencing, using two dedicated cell-free DNA blood tubes. The report covers the germline and somatic variants detected; interpretation rests with the clinical team requesting the test, together with genetic counselling where appropriate.
Frequently asked questions
Can a liquid biopsy replace a tissue biopsy?
Generally not. Tissue biopsy remains the reference standard for diagnosing cancer. A liquid biopsy complements it: it is useful when tissue is unavailable or hard to obtain, to look for mutations with targeted treatments, or to follow the course of the disease.
Can a liquid biopsy detect cancer before symptoms appear?
This is being researched, including multi-cancer early detection tests in large studies. Its role in screening people without symptoms is not yet established: a negative result does not exclude cancer and a positive one needs confirmation with other tests.
How is a liquid biopsy done?
With an ordinary venous blood draw, usually into special tubes that stabilise cell-free DNA. The laboratory separates the plasma, extracts the DNA and analyses it by sequencing or PCR.
Related terms
- Biomarker
A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, disease processes or responses to a therapeutic intervention. It may be a molecule, a genetic variant or an imaging finding.
- NGS (next-generation sequencing)
NGS (next-generation sequencing) is a family of technologies that read millions of DNA or RNA fragments in parallel in a single run, making it possible to study whole genomes, targeted genes or entire microbial communities at scale.
- Nanopore sequencing
Nanopore sequencing is a third-generation technique that reads single DNA or RNA molecules as they pass through a nanometre-scale pore, by measuring changes in electrical current. It produces long reads and data in real time.
- Genetic variant
A genetic variant is any difference in a person's DNA sequence compared with a reference sequence. Most have no effect on health; some are associated with disease or alter risk.
- PCR and qPCR
PCR (polymerase chain reaction) is a technique that copies a chosen stretch of DNA millions of times so it can be detected. qPCR, or real-time PCR, tracks amplification cycle by cycle, allowing the target to be quantified.
Educational content for healthcare professionals and the general public. It does not replace assessment by a healthcare professional: ordering and interpreting any test is the responsibility of the requesting clinician.
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