3 questions about genetic testing

3

QUESTIONS

FOR GENETIC COUNSELOR JASON SHANDLER

Jason Shandler is a genetic counselor at the Upstate Cancer Center.

1What’s the difference between somatic mutations and germline mutations?

All cancer is genetic in the sense that it is caused by mutations in genes, which result in cells growing out of control. However, those mutations can either be acquired during your lifetime or inherited from your mother or father. If it is the latter, there is a risk to pass the mutation on to your children.

When we perform genetic testing on tumor cells, the test is determining the presence or absence of an acquired mutation, which is a change identified only in that cancer cell. This testing, also known as somatic testing, is often done to guide treatment options; perhaps a specific treatment or drug has been developed that can target the specific mutation found in the patient’s tumor cells. A somatic mutation may arise due to an exposure or a mistake during replication of the genetic information, but it is unlikely to be present in other tissues, such as an egg or sperm.

Mutations present in all of your cells, including egg or sperm, are considered germline mutations. If a mutation is first identified on somatic testing, we must then conduct germline testing to determine if the mutation is present in all of your cells or just in the tumor cells. If the mutation is present in other tissues, it would be considered a germline mutation, and these may be passed on to the next generation.

It is important to make the distinction between a mutation that was acquired (somatic) or inherited (germline) for the purposes of treatment decisions and future cancer screenings in that patient and other family members. Identification of a somatic mutation is one reason someone with cancer may seek care from a genetic counselor for hereditary testing.

2What are the risks of having a germline mutation?

Many of the germline mutations we identify do influence cancer risk. However, each mutation has a different overall risk. Some genes are on the lower end of the risk spectrum, and we are learning a great deal about these as more research is conducted. Other

genes have risks that are better defined, as they have been studied longer. It is important to note that having a mutation does not guarantee a patient will develop a cancer; it is never a 100% risk. We always talk about a sliding scale of risk, where everyone starts with some degree of risk, and we move that up or down, depending on what is identified on genetic testing.

Once someone in the family has been found to carry a germline mutation, all of their first-degree relatives qualify for genetic testing; this includes siblings, children and parents. Each of these relatives has a 50% chance to carry the mutation. If a first-degree relative tests negative for the known familial mutation, then that relative's children cannot inherit the mutation either.

3Who is a candidate for genetic testing?

Genetic testing has changed dramatically in the past 10 to 15 years. We used to only be able to test for a few genes. We are now testing for upwards of 80 genes. While most cancers are not hereditary, there are some “red flags.”

The most important red flag we encounter is age. A young age of onset, such as breast cancer under the age of 45 or colon cancer under the age of 50, is one of the most common indications for genetic counseling.

Another red flag is the presence of multiple cancers in one person. There may be an underlying reason why a single individual has developed cancers in multiple locations; perhaps a mutation was present in all of their cells that contributed to the development of seemingly unrelated cancers.

Other times, we see family histories with cancers over multiple generations. For instance, maybe there was cancer in a grandparent’s generation, and then in the parent’s generation, and now into the patient’s generation. If a person has three or more family members on one side of the family with a breast cancer or related cancer, like ovarian, prostate or pancreatic cancer, then they qualify for genetic testing, as there may be an inherited mutation predisposing the family to cancer beyond random chance.

You can inherit genetic predispositions to cancers from your mother or father, so knowing the cancer history on both sides of the family is equally important. A crucial part of our assessment is to draw a pedigree, or family tree, with information from both the maternal and paternal families. Our patients are sent questionnaires prior to meeting with us, so they have an opportunity to list their personal and family history, including the type(s) of cancer and age at diagnosis. Many patients also use this opportunity to start a conversation with other family members about their cancer history and acquire additional information that may prove useful during our sessions.

Everyone approaches genetic testing in their own way, and we all weigh and react to risk factors and results differently. Ultimately, there is no right or wrong way to pursue genetic testing, and each individual makes their own independent decision. For some, testing positive for a mutation can be a constructive experience, as it helps explain why they have developed their cancer. To these patients, testing may provide reason and understanding. It may also provide immediate benefits for treatment and surgical decisions or guide screening for cancers in other organs. CC