Genomic Testing

While examining your biopsy sample under a microscope, the pathologist may also perform molecular testing that checks certain genes, proteins or other molecules for mutations, which are changes that occur in DNA. Many cancers are caused by genetic mutations. Recent research has revealed that melanoma can be classified into subtypes based on mutations in certain genes.

Genomic testing examines a cancer’s genes, which may reveal mutations that could indicate the cancer’s behavior, how aggressive it might be and if it will metastasize (spread). This information helps doctors choose treatment options. In certain cancers, mutations have been discovered that can be treated with targeted therapy, which is designed for a specific mutation.


Several mutations have been discovered that allow melanoma to be classified into distinct subtypes. These include mutations in the genes BRAF (pronounced BEE-raff), NRAS (pronounced EN-rass), NF-1 and KIT. Around half of all melanomas have BRAF mutations.

Mutations have also been found in some melanomas that affect the proteins created by a gene. Changes in the gene that makes the MEK1 and MEK2 (pronounced meck) proteins increase the growth of cancer cells.

Several targeted therapies are approved by the U.S. Food and Drug Administration to treat some mutations, most specifically BRAF and MEK mutations. Targeted therapies known as MEK inhibitors are approved to treat those mutations. Mutations in the NTRK (pronounced EN-track) gene have also been found in some melanomas, which qualifies them for tumor-agnostic immunotherapy.

Researchers in clinical trials are working to find treatments that target other mutations. However, not all melanomas have these mutations.


Genomic testing may also be used to detect biomarkers, which are substances such as genes or molecules that can be measured in the blood, plasma, urine, cerebrospinal fluid or other body fluids or tissues. They are produced by cancer cells or other cells of the body in response to cancer. Also known as tumor markers, biological markers or molecular biomarkers, they are routinely tested for in certain cancers.

Biomarkers may be prognostic, predictive or diagnostic. A prognostic biomarker provides information about a person’s overall cancer outcome, regardless of therapy, while a predictive biomarker gives information about the effect of a specific treatment approach. Diagnostic biomarkers help determine the type of tumor. Some biomarkers may also help determine how aggressive (fast growing) a tumor is and may predict long-term survival.

With the increase in the use of immunotherapy for melanoma, some biomarkers may be tested to determine if immunotherapy is right for you. Some of the following biomarkers may be tested.

  • Lactate dehydrogenase (LDH) is the only accepted serum biomarker for melanoma, and it is measured to determine if a person has an elevated risk for metastasis. A decrease in LDH has been associated with response to immunotherapy. It is a prognostic biomarker that may be elevated if the cancer has progressed. It is released when melanoma cells are damaged or die.
  • PD-L1 expression may be measured to determine if the tumor cells or immune cells in the tumor’s microenvironment contain a higher level, which may mean that a patient could be a good candidate for immune checkpoint inhibitors. However, testing for this biomarker alone is not sufficient to determine a therapeutic response to immunotherapy in patients with melanoma or other skin cancers.
  • Tumor mutational burden (TMB) is an assessment of the number of genetic mutations in a tumor. It can help doctors determine if a patient will respond to immunotherapy. It is believed that the higher the TMB level, the more likely the patient will be to respond.
  • Tumor-infiltrating lymphocytes (TILs) are a type of immune cell that has moved from the blood into a tumor. They can recognize and kill cancer cells. The biopsy sample will be checked for the presence of TILs. Melanomas with higher numbers of TILs and those with TILs inside the tumor have been shown to have a better prognosis and may respond better to immunotherapy. In addition, some treatments result in higher TILs, and they may be a biomarker for response with these therapies.

Not all patients who receive immunotherapy respond, and research is ongoing to find out why. Scientists are also looking for more biomarkers that may indicate whether a patient is a good candidate for immunotherapy. Biomarkers are expected to be more commonly considered in the future so that immunotherapy is not given to someone who may not respond to it.