The value of cell‐free DNA for molecular pathology

Abstract

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. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The emerging role of stimulator of interferons genes signaling in sepsis: Inflammation, autophagy, and cell death

“…Previous studies suggested that cfDNA could activate PRRs . However, aberrational activation of PRRs could induce an imbalance in the inflammation‐immune network, contributing to sepsis, septic shock, or even death.…”

A DNA-modified hydrogel for simultaneous purification, concentration and detection of targeted cfDNA in human serum

“…Most cfDNA fragments are of 180-200 bp in length, and their levels in the serum are relatively low because of their rapid clearance by the spleen, liver, and kidneys. 2,11,16 This makes it challenging to study cfDNA by gel electrophoresis. Therefore, it is necessary to concentrate cfDNA before conducting any studies.…”

“…15 A high isolation efficiency is vital for a successful cfDNA analysis, particularly in early cancers, as the level of cfDNA has been reported to be correlated with the cancer burden. 16,17 Similarly, the fragment size, which is dependent on the cellular release mechanisms, should be considered while analyzing the serum cfDNA. 2,18 Detection of the specic DNA changes, such as in MYCN sequences, MSI, and LOH in cfDNA, associated with cancer has been reported to be an effective method for cancer diagnosis.…”

ctDNA Detection in Microfluidic Platform: A Promising Biomarker for Personalized Cancer Chemotherapy

“…Circulating cell-free DNA (cfDNA) is degraded small DNA fragments found circulating freely in the bloodstream (plasma and serum) and other body fluids. It is mostly double-stranded extracellular molecules of DNA with smaller fragments around 70 bp to 200 bp which do not necessarily originate from the tumor [11,12]. Based on earlier studies, researchers found that the presence of cfDNA is significantly higher in cancer patients compared to healthy patients.…”