Somatic and Germline Cancer Testing

Genetic testing looks for specific changes (mutations) in a person’s genetic information. “Genes,” “DNA,” and “chromosomes” are all genetic information. Genetic information tells a person’s body how to grow and function. All people have genetic changes, which makes everyone unique. Some changes can affect health and development.

Cancer genetic testing looks for mutations in cells with cancer (somatic) and cells without cancer (germline). Genetic mutations can have different effects on your health:

• Harmful (can make you sick or cause health problems)
• Beneficial (can be helpful or protective from health problems)
• Neutral (no effect)
• Uncertain effects

Genetic mutations in cells with cancer (somatic) can sometimes give doctors information about how to treat the cancer. Mutations that are identified in cells without cancer (germline) may be associated with health problems passed down from a parent (inherited). These can make someone more likely to have cancer and other health risks. Overall, inherited mutations are thought to play a role in about 10% to 15% of all cancers.

Somatic mutations are changes that happen to the genetic information in cells after a person is conceived. They are not passed down from a parent. They can happen to almost any cell of the body. The mutations can cause cancer, but not always.

Somatic testing is usually done after a person has been diagnosed with cancer. It looks for genetic mutations in tumor or cancer cells. For some types of cancer, it can help doctors find out more about the cancer, including:

• Information on an exact diagnosis
• Information about the outlook (prognosis) of the cancer
• If treatments are available for cancer with that specific mutation

Usually, mutations in cancer cells are only in those cells. They are not in the rest of the cells of the body. Somatic genetic tests look for gene changes only in cancer cells. These tests are not intended to give information about cancer risk passed down from a parent (inherited).

No, somatic testing does provide information on whether mutations were inherited but may indicate whether additional testing is needed. Testing another sample without cancer, such as cells from your blood or skin, may be needed to see if a mutation is inherited.

Germline mutations are a genetic change in all of the cells in your body. These changes usually happen before conception and can be, but are not always, passed down from a parent.

Germline testing is done on cells that do not have cancer. It is done to see if a person has a gene mutation that is known to increase the risk of developing cancers and other health problems. This test uses cells (such as blood or skin cells) that do not have any cancer cells. Germline mutations can sometimes be passed down from parents.

Your healthcare team may recommend germline testing for you or your child if cancer cell (somatic) testing finds a mutation. This helps your doctor see if the mutation is in all the cells of the body, or just the cancer cells.

Children have a cancer predisposition syndrome when they are born with a gene change that increases their chances of developing cancer. It does not mean a child will have cancer (or a second cancer), but they are at greater risk compared to other children. Germline testing can diagnose a cancer predisposition syndrome.

Chromosome tests look for extra or missing pieces of chromosomes. Chromosomes are packages of genes or DNA. Finding extra or missing copies of genetic material can sometimes help a doctor diagnose and treat the cancer. A cancer microarray and karyotype are 2 types of chromosome tests. They can’t find all differences in a person’s genetic information.

Gene tests, also called molecular tests, look for mutations in genes. Genes are small pieces of genetic information found in chromosomes.

Normal/Negative: This result means that the test did not find any changes in the tested genes. This could mean that you:

• May be less likely to have a cancer predisposition syndrome
• Are not a carrier of the specific genetic mutation
• May need more tests. 1 kind of test cannot look for every possible genetic change

A normal/negative test does NOT get rid of the possibility that you have a cancer predisposition syndrome.

Abnormal/positive: This result means that a change was found in the tested genes. This usually will:

• Identify an increased risk for developing certain cancers (cancer predisposition syndrome) and other health problems
• Confirm that you are a carrier for a disorder
• Recommend other family members be tested for the same genetic change.

A *de novo mutation, also called a new mutation, is a genetic change that happens for the first time in only 1 family member. A de novo mutation may explain genetic disorders when there is no family history of the disorder and the child with cancer has a mutation in every cell in their body, but the parents do not have the same mutation.

Variant of uncertain significance (VUS): This result means that the test found a genetic change, but there is not enough known about the change to give a diagnosis. In some cases, testing other family members can help us understand what the genetic change means. It is more common to find this test result when many genes are tested at once (panel test). Finding a VUS does not typically change medical management recommendations. Your doctor will make recommendations based on personal and family history of cancer until more is learned about the VUS.

Unexpected/incidental result: A genetic test may find an important change that is not directly related to the reason for testing.

Other results: Genetic testing can also provide information on the biological relationships in a family. Examples of this include:

• Finding that the stated father of an individual is not the biologic father
• Finding that the parents may be biologically related to each other

Genetic tests are often expensive, and insurance may not pay for them.

You may have to pay for the test yourself if the test is not pre-authorized. To learn more, read our handout “Insurance Coverage for Genetic Testing” seattlechildrens.org/pdf/PE2051.pdf.

A genetic counselor is available to talk about cancer genetic testing with you. Ask your provider for more information about a referral to a genetic counselor.