Transform Precision Oncology Management with Liquid Biopsy

Going with the Flow:

Liquid Biopsies for Non-Invasive Cancer Screening

Confirmation of a cancer diagnosis typically relies on the results of a tissue biopsy, an invasive surgical procedure to collect a piece of solid tissue from a suspected tumor. However, tissue biopsy may not be feasible due to an inaccessible tumor site or a patient’s inability to tolerate the painful and sometimes risky procedure.’ For cancer tissues that can be biopsied, the resulting sample may not be of sufficient quantity or quality to enable accurate genomic testing or comprehensive biomarker profiling that can guide clinical decisions.

Increasingly, liquid biopsy is being used as a non-invasive, convenient, yet highly sensitive alternative to tissue biopsy for the diagnosis and molecular characterization of cancer.

Liquid biopsy enables the collection and isolation of cell-free DNA (cDNA) from blood plasma or other body fluids.

Molecular testing of cDNA for known cancer genetic markers may reveal the presence of circulating tumor DNA (cDNA) and the detection of specific genomic mutations can help guide clinical decisions. Liquid biopsy enables researchers and clinicians to characterize cancers in a manner that is faster and less invasive than tissue biopsy and that facilitates continual monitoring.

Case Study:

Liquid Biopsy in Prostate Cancer

Read More
For prostate cancer to spread throughout the body, it must enter the bloodstream. Liquid biopsy can be used to screen for circulating tumor cells (CTC) or cDNA as an indication of active disease. Tumor-associated DNA is sequenced for the presence of mutations that may influence treatment. Currently, there are commercially available liquid biopsy tests for prostate cancer that use cDNA for the detection of BRCA2 mutations and mismatch repair enzymes? These tests are used to determine if patients are eligible for therapies such as PARP inhibitors like olaparib and pembrolizumab. Assays such as the PSMA (prostate specific membrane antigen) assay, look for the presence of PSMA CTC expression. Clinical trials using liquid biopsy to measure and monitor response to PSMA-targeted therapies are on-going. 3

How liquid biopsy testing with NGS can aid researchers and clinicians

Fast turnaround of results

→  Rapid profiling of aggressive tumors and advanced disease

Companion Diagnostics

→  Identifying actionable alterations in tumors where tissue biopsy is not possible
→  Measuring tumor heterogeneity and disease burden

Monitoring for response to therapy

  Determining efficacy of treatment
  Analyzing potential resistance mutations during treatment

Monitoring for residual disease

  Assessing remission or progression of disease


  Early detection of cancer prior to disease development

Emerging clinical guidelines for the use of liquid biopsy

Cancer type Guidance
(Organization, version)
Guidance on when to use cDNA / liquid biopsy for the specific cancer type
cDNA is recommended in advanced/metastatic disease
Ovarian NCCN
Molecular analysis may be performed on cDNA when tissue-based analysis is not clinically feasible
Prostate NCCN
When a metastatic biopsy is unsafe or not feasible, cDNA assay is an option, preferably collected during biochemical (PSA) and/or radiographic progression in order to maximize diagnostic yield.
Breast NCCN
Tumor tissue or plasma-based cDNA assays may be used and each of these have benefits and limitations for diagnosis and disease progression. Tissue-based assays have greater sensitivity, but cDNA may reflect tumor heterogeneity more accurately. If one specimen is negative for actionable biomarkers, testing on the alternative specimen can be considered.

*Non-Small Cell Lung Cancer

Don’t let clonal hematopoiesis CHIP away your treatment success

Clonal hematopoietic mutations of indeterminate potential (CHIP) is a common cause of false-positives in cDNA testing when assessing genes that routinely carry CHIP variants. Genes mutated in CHIP partially overlap with genes that drive the growth of solid tumors (e.g. TP53, ATM), so it can be difficult to distinguish between tumor-derived somatic mutations and CHIP in certain genes. 4

False positives can be greatly minimized, however, by simultaneously sequencing the white blood cell (WBC) DNA collected in the buffy coat layer of a patient’s blood sample. WBC DNA sequenced along with the cell-free DNA collected in plasma, or by paired sequencing with a tumor tissue sample, can enable CHIP mutations and germline mutations to be excluded during analysis.’ Despite these benefits, many commercially available assays for clinical use in the US and Europe only analyze plasma DNA.4 The addition of normal WBC DNA sequencing is available with little additional costs, as low-depth sequencing is enough to enable accurate characterization.

The detection of clinically-relevant genetic alterations can be enhanced using analyses that eliminate CHIP noise. This filtered data can better enable treatment decisions.

Clonal hematopoietic mutations of indeterminate potential (CHIP)

Somatic mutations accumulate in cells with a haematopoietic lineage (CHIP) as we age or in response to environmental influences. Genes most often affected include those that drive growth of solid tumors (ie, DNMT3A, TET2, ASXL1, JAK2, PPMID, SF3B1, SRSF2, and TP53). These CHIP mutations can be detected in the plasma and wrongly attributed to solid tumor origins.4,7

“Laboratories should interpret variants identified in genes associated with CHIP cautiously and consider matched white blood cell sequencing with cDNA testing to avoid falsely identifying CHIP variants as somatic mutations derived from the tumor.”

“CHIP is a common cause of false positives in cDNA testing, when interrogating genes that commonly harbour CHIP variants. For clinically actionable testing of tumour suppressor genes such as DNA repair genes, synchronous profiling of plasma DNA and WBC DNA is recommended.”4

Tumor-Normal Matched Liquid Biopsy Wet Lab Workflow

Simultaneous sequencing of plasma cell-free DNA and WBC DNA from buffy coat enables exclusion of CHIP noise from the analysis.

Liquid Biopsies for Non-Invasive Cancer Screening

Additional Resources

Learn about the clinical applications of liquid biopsy and why the right analytical technologies are needed when searching in a sea of genomic data.

Explore precision medicine as we define its significance, uncover current gaps, and shed light on key areas shaping its future.

Learn more about SOPHIA GENETICS and our mission to provide insights that support discovery, treatment decisions, and drug development efforts.


1 Marrugo-Ramírez J, Mir M, Samitier J. Int J Mol Sci. 2018;19(10):2877.

2 Worthington, J.F. Prostate Cancer Foundation. Liquid Biopsy: Catching Cancer Cells in Blood. 18 Jun 2023.

3 Hamid, A. et al. J of Clin Oncol., June 2023; 41(16_suppl)

4 Pascual J, Attard G, Bidard FC, et al. Ann Oncol. 2022;33(8):750-768. (ESMO)

5 Heitzer E, van den Broek D, Denis MG, et al. ESMO Open. 2022;7 (2): 100399. (NSCLC)

6 Brannon, A.R. et al. Nat Comm. 2021; 12:3770.

7 Lockwood, C.M. et al. J Mol Diagn. 2023; 25 (12): 876-897.

Get in touch to find out more

Our client services team is on hand to answer any questions or schedule your live demo.