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
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How liquid biopsy testing with NGS can aid researchers and clinicians
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 |
|---|---|---|
| NSCLC* | NCCN v2.2024 | cDNA is recommended in advanced/metastatic disease |
| Ovarian | NCCN V1.2024 | Molecular analysis may be performed on cDNA when tissue-based analysis is not clinically feasible |
| Prostate | NCCN v1.2024 | 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 v1.2024 | 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)
“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.
References
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.
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