Understanding the Genomics and Genetics of Cancer


Treating cancer is no longer one size fits all. Doctors now know that cancer is as unique as the person who has it because cancer forms when genes begin to change, or mutate, within the structure of normal cells. Therefore, cancer is ultimately a disease of our genes, which are pieces of DNA — the information plan for the growth and control of cells. And one key to understanding and treating cancer is through genomic testing.

Also known as molecular testing or tumor profiling, genomic testing is performed in a laboratory on samples of tumor tissue or blood. This type of testing allows doctors to learn about the tumor’s genome, which is a complete set of its DNA. By unlocking the DNA code of the tumor, doctors can better understand its unique characteristics. Genomic testing is not performed for every person or cancer type. In the cases where this testing has a clinical benefit, some of the potential uses include the following:

  • Diagnosing and staging a cancer
  • Determining prognosis (outlook)
  • Evaluating whether therapies are available to treat mutations in that specific cancer 
  • Choosing treatment
  • Monitoring treatment effectiveness
  • Watching for progression or recurrence
  • Predicting how the tumor might behave, such as how fast-growing it is and how likely it is to spread (metastasize)

This approach to treating cancer is more personalized and precise than traditional treatment strategies. Benefits of using genomic testing include delivering a more accurate diagnosis, selecting more precise treatments and sparing people with slow-growing disease from aggressive treatments that could have many side effects.

This guide focuses primarily on explaining what genomic testing is in an easy-to-understand way, and it offers a brief explanation of genetic testing.

What are mutations?

The foundation of genomic testing is built on finding mutations (changes that occur in the DNA of a cell). It is important to understand that just as every person has a specific mix of genes that are unique to them, cancers are driven by a mixture of specific mutations.

Mutations are generally described as one of two types. They can be acquired during a person’s lifetime from environmental factors, such as tobacco use, ultraviolet radiation, viruses and age; or they are hereditary (inherited from a parent).

Acquired mutations are the most common cause of cancer. These mutations may be caused by mistakes during cell division or by exposure to DNA-damaging agents in the environment. They can be harmful, beneficial or have no effect. Certain mutations may lead to cancer or other diseases. A mutation is sometimes called a variant.

Testing for acquired and inherited mutations through genomic and genetic testing is changing how doctors look at and treat cancer. By using new advanced technologies, doctors can now find mutations in the genes that are causing your specific cancer. This approach to treating cancer is also known as precision medicine or precision oncology.

What is Genomic Testing?

Genomic testing for cancer developed as a result of the Human Genome Project. This project was led by an international team of researchers attempting to sequence and map all of the genes – together known as the genome – of humans.

Sequencing is a process that scientists use to determine the order of the four chemical building blocks – called “bases” – that make up the DNA molecule. DNA refers to the molecules inside cells that carry genetic information that is passed from one generation to the next through offspring. Almost every cell in the body contains a complete copy of the genome, which contains all the information needed for a person to develop and grow.

Genomic testing is typically performed during the diagnostic process 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.

Testing for biomarkers 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 your treatment strategy (see Table 1).

It can also be done during treatment or if the cancer returns. When a tumor returns, it may have different mutations than before, which may affect 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. This testing is usually performed on tumor tissue (biopsy) and sometimes blood (liquid biopsy). Liquid biopsies test a sample of blood to identify circulating cancer cells shed from the tumor or pieces of DNA from the tumor, and check those cells for mutations. Liquid biopsies are increasingly being used because of the ease and convenience of taking a blood sample versus a tissue sample. Tissue and liquid biopsy results are included in the pathology report.

Selecting Treatment

Understanding the types of mutations your tumor has will help you make informed decisions with your doctor about your 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 biomarker for which a specialized treatment exists, standard of care and clinical trials will be the options to consider. Ongoing trials are investigating treatments for more mutations, which may offer patients the chance to receive leading-edge therapies.

When genomic testing is used to select a specific treatment option, the results help doctors determine whether a person may benefit from certain types of drug therapy.

Targeted therapy is a form of systemic therapy that targets genes, proteins or other factors that support the tumor. Genomic testing is used to determine whether any of the known targets in a person’s cancer exist that may respond to this treatment.

Immunotherapy uses the power and complexity of the body’s natural immune system to find and attack cancer cells. The goal is to target cancer cells exclusively, leaving healthy cells alone. Special testing helps determine whether a patient is a candidate for certain types of immunotherapy.

Chemotherapy travels through the bloodstream and affects cells all over the body. Because healthy cells as well as cancer cells are affected, some genomic tests are used to determine whether a person’s cancer will respond well to chemotherapy.

Hormone therapy blocks the stimulating effect of hormones. Genomic testing is used in cancers where hormones may be driving the cancer to determine whether hormone therapy may be helpful.

Table 1 - How Biomarkers are Used

Purpose Description
Screening Most biomarkers are not useful for screening; only 1 biomarker (prostate-specific antigen) is used for screening
Aid diagnosis Biomarkers can help identify the type of cancer when considered along with other clinical factors, such as symptoms and findings on imaging studies
Determine prognosis Some biomarkers are factors considered when determining prognosis or predicting the outcome
Guide treatment Some biomarkers can provide information about the types of treatment that are more likely to produce a response
Monitor response to treatment Biomarkers can monitor the effectiveness of treatment, especially for advanced cancers
Detect recurrence or progression One of the primary uses of biomarkers; if the level of a tumor marker is elevated before treatment, is low after treatment and then begins to increase after treatment, it is likely that cancer is recurring or progressing

Understanding Genetic Testing

The words genetic and genomic are often used interchangeably, but they have different goals and outcomes. Genomic testing is used to understand your cancer for diagnosis, staging and treatment purposes, while genetic testing helps determine whether you have inherited a mutation that increases your risk for developing certain types of cancer — even if you have not been diagnosed with cancer.

Genomic testing is performed on a tumor sample or a liquid biopsy, and genetic testing may be done with a saliva or blood sample.

Several types of cancer, including breast, ovarian, thyroid, prostate, pancreatic, kidney and stomach cancers, as well as melanoma and sarcoma, are known to run in families. 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, it is important to understand that 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.

The following risk factors may indicate that you have inherited an abnormal gene:

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

Though some genetic tests are available to purchase without your doctor’s involvement, they are not recommended for a person who may have cancer. The sensitivity of these tests is unknown compared to those used by doctors and designated laboratories, and the tests may not screen for all the possible genes and mutations for a particular cancer. The laboratories doctors use are regulated by the Clinical Laboratory Improvements Amendments program to meet standards for accuracy and reliability.

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 guide you through the testing process so you understand what the results mean for you, your family members and their future health. Family members may be offered genetic testing if a mutation is found.

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 whether your health insurance will pay for the cost of the test.

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 acceptance, relief, hope, confusion, denial, anger and guilt. Each relative must make the decision about what to do with the information.

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 to refer one that may be nearby.