ctDNA


ctDNA (circulating tumor DNA) are small fragments of genetic material (DNA) released into the bloodstream by cancer cells. All cells in the body shed bits of DNA when they die, but ctDNA comes specifically from tumor cells. Because these DNA fragments carry the same genetic changes as the tumor, they can be analyzed to learn more about the cancer without having to take a tissue sample directly from the tumor.

Where does ctDNA come from?

As cancer cells grow and divide, some of them die naturally or are destroyed by the immune system or cancer treatments. When these cells break apart, they release their contents—including DNA—into the blood. A small amount of DNA is present in everyone’s blood, but ctDNA makes up only a fraction of this total cell-free DNA (cfDNA). Detecting ctDNA requires specialized laboratory techniques that can identify tumor-specific genetic changes.

Why do doctors test for ctDNA?

Testing for ctDNA can help in many parts of cancer care, including:

  • Diagnosis: In some cases, ctDNA testing can help detect the presence of cancer or guide where further investigation is needed.

  • Treatment planning: ctDNA can reveal specific genetic mutations in the tumor that may be targeted by certain therapies.

  • Monitoring response to treatment: Falling ctDNA levels after treatment can indicate that the cancer is responding.

  • Detecting recurrence: Rising ctDNA levels after treatment may be an early sign that the cancer has returned, sometimes before it can be seen on scans.

  • Tracking genetic changes over time: Tumors can evolve and develop new mutations; ctDNA testing can capture these changes without the need for repeat surgical biopsies.

How is ctDNA testing performed?

ctDNA testing is usually done using a liquid biopsy—most often a blood draw from a vein in your arm. The blood sample is sent to a specialized laboratory, where advanced techniques such as next-generation sequencing (NGS) or PCR are used to detect and measure tumor-specific genetic changes in the DNA fragments.

What genetic changes can ctDNA testing detect?

ctDNA tests can look for many of the same mutations found in a tissue biopsy. Common examples include:

  • EGFR, ALK, ROS1, and MET changes in lung cancer.

  • KRAS and NRAS mutations in colorectal cancer.

  • BRAF mutations in melanoma and other cancers.

  • PIK3CA mutations in breast cancer.

  • BRCA1 and BRCA2 changes in certain cancers, including ovarian and prostate cancers.

The exact genetic changes tested will depend on the type of cancer and the test ordered by your doctor.

How are ctDNA results reported?

Your ctDNA results may be described as:

  • Mutation detected: A specific cancer-related genetic change was found, often with details about the gene and mutation type.

  • No mutation detected: No targetable genetic changes were found in the sample.

  • Variant of uncertain significance (VUS): A genetic change was found, but it is not yet clear whether it is related to cancer or affects treatment.

  • Quantitative result: Some tests report the amount of ctDNA present, which can be tracked over time to monitor changes.

Limitations of ctDNA testing

While ctDNA testing is a powerful tool, it has some limitations:

  • Not all tumors release detectable DNA into the blood, so a negative test does not always mean there is no cancer.

  • Tissue biopsy is still needed in most cases to confirm a diagnosis and provide other important information about the tumor.

  • False negatives and false positives can occur, so results are always interpreted in the context of your overall clinical picture.

Questions to ask your doctor

  • Why are you recommending ctDNA testing for me?

  • What genetic changes will this test look for?

  • How will the results affect my treatment plan?

  • Can this test be repeated to monitor my cancer over time?

  • Will I still need a traditional tissue biopsy?

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