Understanding the Genetics and Genomics of Cancer


For more than a century, doctors have studied how cancer develops and how to treat it. After decades of research, doctors know that many cancers are caused by mutations (changes) in a cell’s DNA, which is a person’s genetic blueprint. By understanding DNA, doctors have a better idea about how genes interact with each other and function or malfunction. Unlocking these mysteries of the human genome has dramatically impacted how doctors treat many types of cancer today.

This knowledge enables doctors to use genomic and genetic testing to help prevent and treat cancer.

This guide is designed to make a very complicated subject as easy to understand as possible. Though mutations can come in many forms and may be called by many names, such as alterations or fusions, for the purposes of this guide we will refer to them as “mutations.”

Although genomics and genetics sound similar, they are not. Genomics is the study of the complete set of DNA base pairs (the DNA sequence) including all
of the genes of a person’s normal cells and tumor cells. Genomic testing is conducted to determine the genetic mutations present within the tumor, which may help identify specific treatments. This testing is usually performed on tumor tissue and sometimes blood. Liquid biopsies test a sample of blood to look for circulating cancer cells shed from the tumor or pieces of DNA from the tumor to test for mutations. Liquid biopsies are increasingly being used because of the ease and convenience of taking a blood sample versus a tissue sample.

Genetics is the study of genes and the passing of genetic information and traits from parents to children (heredity). Genetic testing is used to look for inherited genes that may indicate an increased risk of developing cancer during a person’s lifetime. It may be performed before or after someone is diagnosed with cancer. The normal cells present in samples of blood and/or saliva are commonly used to isolate DNA for these tests.

This content focuses on understanding genomic testing and the role it plays in the diagnosis and treatment of cancer.

Understanding Genomic Testing

Genomic testing is used to examine a cancer’s genes to identify mutations that could indicate the cancer’s behavior, how aggressive it might be and if it will metastasize (spread). This information can lead to a more precise diagnosis and a more personalized treatment plan.

This offers the possibility of treating the cancer more effectively without damaging healthy cells. It also spares people with slow-growing disease from aggressive treatments that may have many side effects.

Doctors use genomic testing for many different reasons.

  • Diagnosing and staging a cancer
  • Determining prognosis (potential for fast growth and metastasis or slow growth)
  • Choosing the most effective treatment for each cancer
  • Checking whether the tumor is responding to treatment
  • Monitoring for progression or recurrence

Understanding the types of mutations your tumor has will help you make informed decisions with your doctor about your treatment options. A variety of tests are used to find genomic mutations, and the tests your doctor chooses may depend on the type of cancer you have and the known mutations associated with it (see Genetic Testing).

These tests are typically performed during the diagnostic process but can also be done during treatment or if the cancer returns. When a tumor returns, it may have different mutations than before and they may affect treatment options.

If a mutation is found, your doctor will select a treatment that may target your cancer’s specific mutation. But not all mutations have uniquely approved treatments available. If the testing does not identify a specialized treatment, standard of care and clinical trials will be the options to consider. Trials are ongoing to find treatments for more mutations and may offer the chance to receive leading-edge therapies.

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. Biomarkers are produced by cancer cells or other cells of the body in response to cancer. They are routinely tested for in certain cancers. Some biomarkers may also help determine how aggressive (fast growing) a tumor is and may predict prognosis (outcome). When doctors test for biomarkers, it is known as molecular testing. This type of testing is not used for every cancer diagnosis. Your doctor will talk with you if it may be beneficial for you (see Table 1).

Qualifying For Specific Treatments

The results of genomic testing help doctors determine whether a person may benefit from targeted therapy or immunotherapy. Many mutations are treated by targeted therapies, a type of systemic therapy that targets specific problems with genes, chromosomes, proteins, enzymes and other molecules involved in the development and growth of cancer (see Treatment Options).

Targeted therapies work in different ways to 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.

Biomarkers may also be tested to determine whether you are a candidate for immunotherapy, which uses the immune system to find and attack cancer. These 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 be a good candidate for a type of immunotherapy called 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 will be to respond to immunotherapy.
  • Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). MSI-H describes cancer cells that have a higher-than-normal number of genetic markers called microsatellites, which are short, repeated sequences of DNA. dMMR occurs when a cell loses its ability to correct errors made during cell division when DNA is copied. These mutations may qualify you for some types of immunotherapy.

Genetic Testing

More people are familiar with the idea of genetic testing because it has been the focus of many news reports and advertisements for home-based testing kits. In terms of cancer, doctors use genetic testing to determine whether you have inherited a mutation that increases your risk for developing certain types of cancer, including breast, ovarian, thyroid, prostate, pancreatic, kidney and stomach cancers, as well as melanoma and sarcoma.

If you have a family history of a particular type of cancer, you may consider genetic testing to find out whether you carry the corresponding gene. However, if you have inherited a mutated gene, it doesn’t mean you will automatically develop cancer; it only means the risk is increased and you can explore ways to lower it, such as surgery, medication, frequent screenings or lifestyle changes.

Doctors look for certain risk factors that may indicate a hereditary cancer is possible:

  • Family history of cancer
  • Cancer at an early age
  • Multiple cancers in one relative
  • Rare cancers
  • Ancestry, such as Ashkenazi Jewish heritage

Genetic Counseling

Special training enables a genetic counselor to guide you and your family members before and after you have genetic testing. The genetic counselor will discuss your medical history and cancer screening history, your family’s cancer history, the possibility of an inherited cancer risk, the benefits and limitations of genetic testing, and current laws regarding the privacy of genetic information. The counselor can also help find out if your health insurance will pay for the cost of the test.

Depending on the resources available at each cancer institution, it is important to know that a cancer genetic counselor may not be available. If one is not available at your cancer center, ask your nurse navigator if you can be referred to one that may be nearby.

Before meeting with a genetic counselor, gather the following information if it is available:

  • Medical records, doctor notes and pathology reports
  • List of family members, including current ages or age at death and cause of death
  • Specific cancers diagnosed within the family

Your genetic counselor will help you understand your test results and their potential effect on you and other family members, and provide counseling and support. Family members may be offered testing if a mutation is found.

The Importance Of Sharing Your Family Health History

Choosing to have genetic testing is a decision that affects your entire family. Knowing and sharing the information could help them be screened and monitored closely if they have a gene mutation associated with cancer. Preventing or detecting a cancer early offers the best chance of a successful treatment outcome.

The results may be complicated and difficult to interpret. A genetic counselor can be crucial to help you understand what the results mean for you and your family and their future health.

Once you understand your results, you can choose to share them with your children, siblings, nieces, nephews, etc. However, be prepared that they may not want to know or do anything about the information. Learning these results can bring up a range of emotions, including feelings of acceptance, relief, hope, confusion, denial, anger and guilt. Each must make the decision about what to do with the information.




Questions To Ask Before Testing

  • How do I know if I need genomic or genetic testing?
  • Is genomic testing available for my type of cancer?
  • What are the risks and benefits of genomic testing?
  • Will you use a blood or tissue biopsy to do the testing?
  • When would this testing occur?
  • Will the results affect how the cancer is treated?
  • What happens if I don’t have a mutation?
  • What if I have a mutation that doesn’t have an approved treatment?
  • Will insurance cover the cost of testing?
  • Who will help me understand the results of my testing?