Circulating Tumour DNA and Melanoma

By: Jhanavi Srivastava, Woodlawn High School

What is Melanoma?

The cells that make melanin, the pigment responsible for your skin's colour, grow into melanoma, one of the most dangerous types of skin cancer. Additionally, melanoma can develop in your eyes and, very rarely, inside your body, like in your throat or nose. It can start in a mole (skin melanoma), but it can also begin in pigmented tissues like the intestines or the eye.

The precise explanation for why all melanomas occur is unknown, although exposure to ultraviolet (UV) radiation from sunshine, tanning beds, or tanning lamps increases your risk of getting the disease. Limiting your exposure to UV light reduces your chance of developing melanoma.

Main symptoms/ signs of melanoma:

  1. The shape of a mole's two halves differs from one another.
  2. A mole's edge is uneven or irregular. It may appear angular, notched, or fuzzy. The colour could bleed into the mole's surroundings.
  3. A mole's colour varies from area to area. It might come in tan, brown, and black tones. There are also occasionally visible blue, grey, red, pink, or white regions.
  4. Approximately the size of a pencil eraser, a mole is greater than 6 mm (1/4 inch) in diameter.
  5. The mole has changed in colour, size, form, or texture. The mole could itch, and you might experience burning or tingling sensations.

Other melanoma skin cancer symptoms include:

  1. a wound that is not healing
  2. an oozing or bleeding mole or sore
  3. skin that has broken and ulceration

Stages of Melanoma

Figure 1: Visual comparisons of different stages of melanoma.


What is Circulating Tumour DNA? (Analysis)

Circulating tumor DNA (ctDNA) refers to single-stranded or double-stranded DNA released into the bloodstream by tumor cells, carrying the tumor's mutations. It holds potential as a diagnostic tool for cancer. Identifying tumor-derived ctDNA, also known as circulating tumor DNA (ctDNA), provides a non-invasive means to access the genetic makeup of the tumor. This aids in diagnosis, informs therapeutic approaches, and tracks therapy effectiveness. Nevertheless, due to the association between ctDNA signal and NGS (next-generation sequencing) noise, the current use of circulating cell-free DNA (ccfDNA) for somatic mutation discovery is primarily limited to tumor-informed searches and identification of common variants.

What is the link between Melanoma and ctDNA?

Accurate cancer prognosis assessment is crucial in the era of precision medicine for risk classification and optimal treatment selection. Circulating tumor DNA (ctDNA) can detect alterations in genes. For several cancers, ctDNA released into the bloodstream by cancer cells provides a complementary or alternative source of tumor DNA to traditional tumor tissue DNA.

In the realm of melanoma, ctDNA offers personalized management tools during treatment. By furnishing a reliable and accessible method to determine a patient's illness status, ctDNA facilitates swift, accurate treatment decisions, optimizing efficacy while minimizing unnecessary treatment burden. Its longitudinal collection allows for early and dynamic evaluation of therapy response.

Available Tests

Tests of Melanoma Skin Cancer include:

  1. Physical examination and medical history. (A dermatologist may be suggested)
  2. A skin biopsy may be performed using the following techniques: shaving (tangential), punch biopsy, excisional and incisional biopsies, fine needle aspiration (FNA), surgical (excisional) lymph node biopsies, or sentinel lymph node biopsies.
  3. Lab tests on biopsy samples
  • Comparative genomic hybridization (CGH)
  • Gene expression profiling (GEP)
  • Immunohistochemistry (IHC)
  • Fluorescence in situ hybridization (FISH)
  1. Imaging Tests
  • Ultrasound
  • CT-scan
  • MRI
  • Chest X-ray (to determine spread in lungs)
  • PET- scan
  1. Blood tests : Before beginning treatment, doctors frequently check the blood for lactic dehydrogenase (LDH) presence. A high LDH level can indicate that the melanoma has progressed to difficult-to-treat areas of the body. This may impact the cancer's stage.
  2. ctDNA as a biomarker

The Significance of ctDNA in Melanoma Research

Circulating Tumor DNA (ctDNA) has emerged as a transformative tool in melanoma research, revolutionizing how we understand, diagnose, and manage this aggressive skin cancer. ctDNA's uses in melanoma research encompass:

  • Early Detection and Diagnosis: Analyzing ctDNA in blood samples detects genetic changes associated with melanoma, facilitating timely diagnosis and interventions at early stages.
  • Real-time Treatment Monitoring: ctDNA provides a minimally invasive method to assess treatment response over time, guiding adjustments if necessary.
  • Residual Disease Detection: ctDNA analysis detects minute tumor DNA in the blood post-surgical removal, identifying residual disease and informing the need for additional treatment.
  • Personalized Treatment: ctDNA profiling identifies actionable mutations, optimizing treatment by matching therapies to the patient's genetic profile.
  • Research Insights and Biomarker Discovery: Studying ctDNA deepens our understanding of melanoma biology, progression, and treatment response, while also uncovering new biomarkers for prognosis and response prediction.

Mutations Involved

Melanoma is one of the most mutated cancers, related largely to its origins in ultraviolet light and other mutational mechanisms.

Figure 2: Mutations in Melanoma and their clinical features (Source)

Available Treatments

Treatment options depend on cancer stage and other factors, including surgery, immunotherapy, targeted therapy, chemotherapy, and radiation treatment. Age, general health, potential treatment benefits, and adverse effects also play crucial roles in precision treatment decisions.

Crucial considerations for precision treatment:

  • Age and general well-being
  • Stage of cancer
  • The possibility that treatment will successfully treat cancer or provide additional benefits
  • The potential adverse effects (side effects) of therapy.

Genes and Mutations in Melanoma

The major genes involved in melanoma include:

  • CDKN2A: Located in Chromosome 9 and its main function is instructing the making of several proteins.
  • p14/ARF: Located on the CDKN2a locus and its main function is to inhibit the course of the cell cycle and triggers apoptosis in order to quell oncogene stimulation.
  • CDK4: Located on Chromosome 12 and its function is to encode a member of the serine/threonine kinase family of proteins. The protein aids in the transition of the G1 to S phases of the cell cycle
  • CDK6: Located on Chromosome 7 and it is the regulator of melanoma tumour angiogenesis, migration, and cell proliferation.


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_By: Jhanavi Srivastava_

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.