Genomic & Genetic Testing
Many cancers are caused by mutations (changes) in a cell’s DNA, and some of those mutations can be tested for and used to develop a more personalized treatment plan.
Genomic testing is a type of molecular testing that looks at the DNA of a tumor. It may include testing for specific genes, proteins or molecules of the tumor and may be used to determine whether genetic mutations are present within the tumor. It is typically performed on the initial biopsy material and is repeated if the cancer recurs. It 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. Biomarkers are produced by cancer cells or other cells of the body in response to cancer.
Molecular testing results can also indicate the cancer’s behavior, how aggressive it might be and whether it will metastasize (spread). This information can lead to a more precise diagnosis and a more personalized treatment plan that offers the possibility of treating the cancer more effectively.
The results of genomic testing help doctors determine whether a person qualifies for specific types of therapy. Many mutations are treated by targeted therapies, a type of systemic therapy that targets specific genes, chromosomes, proteins, enzymes and other molecules involved in the development and growth of cancer. Targeted therapies work in different ways and target various molecules or cellular functions. They can block or turn off signals to cancer cells, prevent cells from living longer than normal and destroy cancer cells.
In addition to testing for BRAF, RAS, NRAS, KRAS and HER2 to determine eligibility for tar-geted therapies, your doctor will also look specifically for DNA errors caused by high microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) to determine eligibility for immunotherapy, an approach that uses the immune system to treat cancer.
The biomarkers tested to determine if you are a candidate for immunotherapy include the following:
- PD-L1 expression: PD-L1 (programmed death-ligand 1) is a protein that acts as a kind of “brake” to keep the body’s immune responses under control. PD-L1 may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. A high level of PD-L1 expression on tumor cells or immune cells in the tumor’s microenvironment may mean you could respond well to immune checkpoint inhibitors.
- Tumor mutational burden (TMB): This is an assessment of the number of genetic mutations in a tumor. It is believed that the higher the TMB level, the more likely you are to respond to immunotherapy.
- Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR): MSI-H indicates an abnormality in the sequence of DNA in microsatellites, which are short, repeated sequences of DNA. dMMR occurs when a cell loses its ability to correct errors made when DNA is copied during cell division. These mutations may qualify you for some types of immunotherapy.
Not all mutations have uniquely approved treatments available. If testing does not identify a specialized treatment, standard of care and clinical trials may be the options to consider.
Identifying hereditary cancers allows people at an increased risk to be monitored more closely for the development of cancer. A family history of a certain cancer may prompt you to be tested to see if you carry the gene. Having an inherited mutation doesn’t mean you will automatically develop cancer; it only means the risk is increased. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common inherited disorder that increases your risk of colorectal cancer. Lynch syndrome also increases the risk for other types of cancer.
Genetic tests are generally ordered by a doctor or other health care provider if there is concern you may have an inherited risk of cancer. Doctors may test for one gene or a small number of genes, which is called single/limited gene panel testing, or many genes, which is called multi-gene panel testing. Typically, a blood or saliva sample is collected and sent to a laboratory for testing. The laboratories are regulated under the Clinical Laboratory Improvement Amendments (CLIA) program to meet standards for accuracy and reliability.
When a multi-gene panel is necessary, next-generation sequencing (NGS) is used to define the DNA sequence of these genes. This technique is capable of processing multiple DNA sequences simultaneously with more speed and accuracy than single-gene tests. DNA sequencing determines the order of the four building blocks of DNA. NGS is performed on both tumor tissue and on DNA in the blood and, at present, can detect abnormalities that may be treated with specific therapies.
Although some direct-to-consumer genetic tests are available, they are not recommended for a person who has cancer, for many reasons. The sensitivity of these tests is unknown compared to those used by doctors and designated laboratories; they typically provide raw data without offering assistance interpreting the results or providing genetic counseling; and the tests may not screen for all the possible genes and mutations for a particular cancer. If you want to learn more about genetic testing, ask your doctor or request a referral to a genetic counselor.