Cell-free DNA (cfDNA) refers to small DNA fragments found in the bloodstream and other bodily fluids, such as spinal fluid and urine. These fragments are derived from various sources, including the breakdown of cells, the release of DNA from damaged or dying cells, and the shedding of DNA by normal cells. The presence of cfDNA in bodily fluids is an indication of various processes that include physical injury, inflammation, and cancer.
How is cell-free DNA (cfDNA) used?
One of the main applications of cfDNA is in the field of non-invasive prenatal testing (NIPT). NIPT is a screening test that can be performed during pregnancy to assess the risk of chromosomal abnormalities in the fetus, such as Down syndrome, Edwards syndrome, and Patau syndrome. NIPT involves the analysis of cfDNA from the mother’s blood, which contains small amounts of the fetus’ DNA. By analyzing the cfDNA, it is possible to identify any abnormalities in the fetal genome.
Another application of cfDNA is in the detection and monitoring of cancer. Cancer cells often release DNA into the bloodstream, and the presence of cfDNA with specific genetic abnormalities can indicate the presence of cancer. The analysis of cfDNA can be used to diagnose cancer, monitor the treatment effectiveness, and detect recurrence after treatment.
In addition to its use in NIPT and cancer diagnosis and monitoring, cfDNA has also been studied for its potential use in diagnosing and monitoring other conditions, such as heart attack, stroke, and autoimmune diseases.
What is non-invasive prenatal testing (NIPT)?
The test is typically performed using a sample of the mother’s blood, collected during the first trimester of pregnancy (usually between 9 and 13 weeks). The blood sample is analyzed for the presence of cell-free DNA (cfDNA) from the fetus at a laboratory. The laboratory first isolates the cfDNA from the mother’s blood sample to perform the test. The fetal cfDNA is then amplified and analyzed using a technique called next-generation sequencing. This involves sequencing short fragments of DNA from many different locations in the genome at the same time. The resulting data is used to determine the presence or absence of specific chromosomal abnormalities in the fetal DNA. The test results are typically available within a few weeks and are reported as a risk score, indicating the likelihood of the fetus having a particular chromosomal abnormality.
Some of the genetic characteristics that are used for NIPT include:
- Chromosomal aneuploidies: These are abnormalities in the number of chromosomes, such as trisomy (an extra chromosome) or monosomy (a missing chromosome). Some common chromosomal aneuploidies that NIPT detects include Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13).
- Structural chromosomal abnormalities: These are abnormalities in the structure or arrangement of the chromosomes, such as deletions (missing pieces) or translocations (chromosomes joined abnormally).
- Single gene disorders: These are genetic conditions caused by mutations in a single gene. Some single-gene disorders, such as cystic fibrosis and sickle cell anemia, can also be detected by NIPT.
NIPT is a screening test, not a diagnostic test, indicating an increased risk of a chromosomal abnormality.
How is cell-free DNA (cfDNA) used to detect cancer?
To detect cancer using cfDNA, a sample of the patient’s blood is collected and sent to a laboratory for analysis. The cfDNA is isolated from the blood sample and amplified using techniques such as polymerase chain reactions (PCR). The amplified DNA is then analyzed using a variety of techniques, including next-generation sequencing, to identify any genetic abnormalities that may be indicative of cancer.
The test results are typically reported as a risk score, indicating the likelihood that cancer is present. If the test results are positive, further diagnostic testing is necessary to confirm the diagnosis.
In addition to its use in cancer detection, the analysis of cfDNA can also be used to monitor the response to treatment and detect the recurrence of cancer after treatment. By analyzing changes in the cfDNA over time, it is possible to track the cancer’s progression and determine the treatment’s effectiveness.
What is circulating tumor DNA (ctDNA)?
Crucial to cancer research and diagnostics, circulating tumor DNA (ctDNA) refers to a small subset of the cfDNA and consists of small DNA fragments released into the bloodstream by cancer cells. ctDNA can be detected in the blood of individuals with cancer and can provide information about the presence and characteristics of the cancer.
Some characteristics of ctDNA include:
- Size: ctDNA fragments are typically smaller than normal DNA fragments; due to the presence of breaks and mutations in the DNA.
- Composition: ctDNA comprises both normal DNA and DNA with mutations or abnormalities. The presence of specific mutations or irregularities in the ctDNA can provide information about the type and characteristics of the cancer.
- Stability: ctDNA is relatively stable in the bloodstream and can be detected for an extended period after it is released from the cancer cells.
- Concentration: The concentration of ctDNA in the bloodstream can vary depending on the stage and size of the cancer.
- Heterogeneity: ctDNA can be highly heterogeneous, meaning it can contain various mutations and abnormalities. This heterogeneity can make it challenging to detect and analyze accurately.
Besides NIPT and Oncology, how is cell-free DNA (cfDNA) used?
In addition to its use in non-invasive prenatal testing (NIPT) and cancer detection and monitoring, cell-free DNA (cfDNA) has also been studied for its potential use in diagnosing and monitoring other conditions. Some examples of areas of research for cfDNA include:
- Heart attack: The analysis of cfDNA has been studied as a potential tool for the diagnosis and prognosis of acute myocardial infarction (heart attack).
- Stroke: The presence of cfDNA in the blood is an indicator of brain injury in stroke patients, and the analysis of cfDNA has been studied as a potential tool for the diagnosis and prognosis of stroke.
- Autoimmune diseases: The analysis of cfDNA is a potential tool for diagnosing and monitoring autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.
- Transplantation: The analysis of cfDNA has been studied as a potential tool for monitoring organ transplantation and detecting rejection.
- Pregnancy complications: The analysis of cfDNA is a potential tool for diagnosing and monitoring complications during pregnancy, such as preterm labor and preeclampsia.