The value of cell-free DNA for molecular pathology

Caitlin M. Stewart, Prachi D. Kothari, Florent Mouliere, Richard Mair, Saira Somnay, Ryma Benayed, Ahmet Zehir, Britta Weigelt, Sarah Jane Dawson, Maria E. Arcila, Michael F. Berger, Dana W.Y. Tsui*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic sites, and ctDNA can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled regularly to monitor response to treatment, to define the evolution of the tumour genome, and to assess the acquisition of resistance and minimal residual disease. Recently, clinical ctDNA assays have been approved for guidance of therapy, which is an exciting first step in translating cell-free nucleic acid research tests into clinical use for oncology. In this review, we discuss the advantages of cell-free nucleic acids as analytes in different body fluids, including blood plasma, urine, and cerebrospinal fluid, and their clinical applications in solid tumours and haematological malignancies. We will also discuss practical considerations for clinical deployment, such as preanalytical factors and regulatory requirements.

Original languageEnglish
Pages (from-to)616-627
Number of pages12
JournalJournal of Pathology
Issue number5
Publication statusPublished - 1 Apr 2018

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