Other Body Fluids as Non-invasive Sources of Cell-Free DNA/RNA

Abstract

In addition to plasma and serum as sources of nucleic acids circulating in the whole body, amniotic fluid, saliva, urine, pleural effusion, bronchial lavage, bronchial aspirates, breast milk, colostrums, tears, seminal fluid, peritoneal fluid, pleural effusion and stools are all available for minimally invasive analysis of nucleic acids. This chapter introduces the possibilities of using nucleic acids from amniotic fluid, saliva, urine, cerebrospinal fluid and bronchial lavage/aspirates in attempts to produce reliable early markers for diagnosis, prognosis and treatment monitoring using minimally invasive methodology. Moreover, the data from amniotic fluid can be used also to further the understanding of normal and abnormal fetal development in utero. In addition, the data from saliva can be employed for monitoring the progress of premature born infants.

Urine cell-free DNA is a biomarker for nephroblastomatosis or Wilms tumor in PIK3CA-related overgrowth spectrum (PROS)

“…Urine cfDNA comprises both transrenal cfDNA and DNA from renal epithelial cell shedding. 10 Transrenal cfDNA comprises 150-200 bp DNA fragments that are filtered from plasma and likely does not contribute a significant portion to the overall quantity of measureable urine cfDNA. 11 Despite a similar epithelial origin of DNA from cellular urine isolates, only two of the three patients with nephroblastomatosis had significant amounts of the variant in their sediment.…”

“…We found high levels of PIK3CA variants in urine cfDNA, and noted that this was correlated with a history of nephroblastomatosis or WT compared to patients without known renal involvement (p=0.0004). Urine cfDNA comprises both transrenal cfDNA and DNA from renal epithelial cell shedding 10 . Transrenal cfDNA comprises 150–200 bp DNA fragments that are filtered from plasma and likely does not contribute a significant portion to the overall quantity of measureable urine cfDNA 11 .…”

Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms

“…Cell-free DNA (cfDNA) is a fraction of circulating nucleic acids (CNAs), which was discovered and first described by Mandel and Metais, in 1948 [1]. The term encompasses all kinds of extracellular DNA molecules found in serum or plasma and other body fluids [2] of vertebrates and includes genomic and mitochondrial host DNA [3,4], as well as foreign DNA [5,6], for example, of bacterial or viral origin. The cfDNA molecules occur predominantly in the form of double-stranded DNA (dsDNA) [7] and are mostly of small size, ranging between 100 and 200 base pairs (bp) [8].…”

Fetal Fraction and Noninvasive Prenatal Testing: What Clinicians Need to Know

“…These cfDNA fragments are released from all organs during a range of cellular processes, including apoptosis, necrosis and microparticle secretion. 1 Circulating plasma cfDNA has been intensively studied for a wide range of noninvasive "liquid biopsy" applications in oncology and general medicine but has had the most impactful translational success in prenatal screening for fetal aneuploidy. 2 Maternal plasma cfDNA contains both maternal and fetal sources of cfDNA (Figure 1).…”