Tumor DNA Sequencing in Cancer Treatment

What is clinical tumor DNA sequencing?

Cancer is a genetic disease—that is, it is caused by changes in DNA that control the way cells function, especially how they grow and divide. These changes can be inherited, but most arise randomly during a person’s lifetime, either as a result of errors that occur as cells divide or from exposure to DNA-damaging carcinogens.

Each person’s cancer has a unique combination of genetic changes, and tumor DNA sequencing—sometimes called genetic profiling or genetic testing—is a test to identify these unique DNA changes.

In some cases, knowledge of the genetic alterations in your cancer can help determine a treatment plan. Some treatments—particularly, some targeted therapies—are effective only for people whose cancer cells have specific genetic alterations that cause the cells to grow out of control (these are sometimes called “driver” mutations).

For example, mutations in the EGFR gene that make cells divide rapidly are found in some people’s lung cancer cells. A patient whose lung cancer cells harbor an EGFR mutation may respond to treatment with drugs called EGFR inhibitors. Clinical tumor DNA sequencing can reveal whether a patient’s lung tumor has an EGFR mutation.

Tumor DNA sequencing is at the crux of precision medicine: care tailored to the molecular characteristics of each patient’s disease.

How do I know if tumor DNA sequencing is right for me?

Consult your health care provider to discuss the possibility of tumor DNA sequencing as part of your care. Tumor DNA sequencing is most common (and most beneficial) for patients with cancer types that may be susceptible to treatment with a targeted therapy. These patients are commonly tested for the genetic mutation the therapy targets. For example, genetic testing is a routine part of care for colorectal and lung cancer.

In addition, some oncologists may recommend tumor DNA sequencing for patients with advanced cancer that is not responding to standard treatment or for which no standard treatment is available. This may help identify other treatments that might be effective given the cancer’s genetic makeup.

In other cases, tumor DNA sequencing may be available to you if you are participating in a clinical trial that includes a sequencing test. Several ongoing precision medicine trials, such as TCH-MATCH and TCH-COG Pediatric MATCH, are using tumor DNA sequencing to assign patients to investigational treatments based on the genetic alterations in their tumors.

How is tumor DNA sequencing done?

If you and your health care providers decide to make tumor DNA sequencing part of your care, they will remove a sample of your tumor and, in some cases, a sample of your healthy cells. They may obtain these samples during surgery, if it is part of your treatment plan. In other cases, you may need to have a biopsy.

Your samples will be sent to a specialized lab, where researchers will isolate your DNA and then use a machine called a DNA sequencer to “read” it. They will then analyze the sequence of your DNA to determine if there are any genetic alterations that make your tumor susceptible to certain treatments. They may also examine the DNA sequence of your healthy cells to determine if you have any inherited, or germline, mutations that increase your risk of cancer and can also influence treatment decisions.

Based on your tumor’s unique genetic alterations, the specialized lab may generate a report that lists treatments your tumor is likely to respond to. Your health care team will discuss the results with you to make a personalized treatment decision.

What kinds of sequencing tests are available?

Illustration of DNA structure

FDA Approves Two Genomic Profiling Tests for Cancer

Tests can identify different cancer-associated genetic alterations.

DNA sequencing tests can have a broad or a targeted focus. Targeted DNA sequencing tests, also called multigene panels, are the most frequently used sequencing test for patient care. These tests analyze specific “driver” mutations. Some targeted sequencing tests analyze alterations that are common in a single cancer type, whereas others analyze alterations that may be found in many cancer types.

Broad DNA sequencing tests analyze the sequence of large regions of DNA rather than specific mutations. For example, whole-genome sequencing reads the sequence of all of the DNA in your cells—what’s known as the genome. Another broad test, called whole-exome sequencing, reads the sequence of all of your genes, known as the exome. Most cancer-causing DNA changes occur in genes, but DNA changes outside of genes can also drive cancer growth. Because whole genome and whole exome tests have not been directly compared, it is not clear if one type of test is more beneficial to patients.

In addition, a quantitative mRNA expression test can also gather information about what treatments may work best for you. For example, one quantitative mRNA test commonly used for cancer care analyzes 21 different genes that can cause breast cancer and predicts whether a patient with breast cancer is likely to benefit from chemotherapy treatment.

What do the results of a tumor DNA sequencing test mean?

Multigene panel tests clearly indicate whether you have a genetic alteration in your tumor that can be targeted by an existing therapy. Because broad tumor DNA sequencing tests analyze more regions of DNA, they may be more difficult to interpret. For example, they may identify genetic alterations that do not cause cancer (benign) or whose effects are not known (of unknown significance). Alterations that are benign or of unknown significance do not aid patient care.

Tumor DNA sequencing tests may also uncover the presence of inherited alterations that increase cancer risk (hereditary cancer syndromes) or that are associated with diseases or conditions other than cancer. These are known as incidental, or secondary, findings. Finding that you carry an inherited genetic alteration may have implications not only for you, but also for your close blood relatives. For this reason, it is important to consult a genetic counselor to help interpret the results of DNA sequencing tests.

What are the limitations of tumor DNA sequencing tests?

Genetic tests do not benefit every patient. For example, they might not identify the DNA alteration that is driving the growth of your tumor. Or they might find such an alteration but it cannot be targeted by existing therapies. And even if you have an alteration that can be targeted by an existing therapy, other unique aspects of your biology (such as how your body breaks down a drug) can influence how you actually respond to the therapy.

Another limitation is that tumors are composed of cancer cells with varied, or heterogeneous, genetic alterations. Therefore, a small sample of cancer cells obtained from a biopsy may not accurately represent a heterogeneous tumor. This could mean that DNA sequencing tests may identify a potential treatment that can act against some, but not all, of your cancer cells. Cancer cells that are not targeted by the treatment have the potential to continue growing, causing the tumor to come back.

In addition, the genetic alterations in a tumor can change over time, but a sequencing test only captures a “snapshot” of the alterations present at one point in time. This means that the results of a sequencing test obtained one year ago may not accurately reflect the genetic alterations present in your cancer cells at this moment.

How much does tumor DNA sequencing cost?

The cost of tumor DNA sequencing varies by the type of test. For example, one commercial test that analyzes genetic alterations in more than 300 genes for patients with solid tumors, currently costs $5,800.

Clinical whole-exome sequencing tests cost between $1,000 and $5,000, and whole-genome sequencing could cost over $10,000. However, biotechnology companies are constantly developing faster and cheaper sequencing techniques that could eventually bring the price down.

Insurance coverage of tumor DNA sequencing depends on your insurance provider and the type of cancer you have. Insurance providers typically cover a DNA sequencing test if there is sufficient evidence to support that the test is necessary to guide patient treatment. Tests without sufficient evidence to support their utility may be considered experimental and are likely not covered by insurance.

Many clinical trials involve tumor DNA sequencing. If you participate in one of these clinical trials, the cost of tumor sequencing might be covered. The study’s coordinator can give you more information about associated costs.