When a patient is diagnosed with cancer, an initial full-panel genetic test can identify hereditary gene mutations. If they carry a mutation, it will be the exact same mutation for everyone else in the family. Armed with this knowledge, these family members require just a “single site” analysis to screen for that particular mutation. This knowledge can save lives.
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Our genetic code can reveal our ancestry, eye color, and even our predisposition to disease, like cancer. Modern technology allows us to examine a number of different genes that may contain cancer-causing mutations. This information can allow men and women the opportunity to prevent or treat cancer more effectively.
In the past, cancer genetic testing utilized Sanger sequencing. This testing involved exon-by-exon sequencing of each suspected gene. Health care professionals would start with the most commonly associated genes and continue to lesser-known genes. For example, a woman with breast cancer was often tested for the BRCA1 and 2 mutations. If that test was negative, the woman could choose, at an additional expense, to look for additional gene mutations. This process was timely and costly. Modern “next generation” sequencing has improved this process. One vial of blood or saliva can provide more information about predisposition and inherited risk than ever before. Gene panels allow 25 or more genes to be sequenced at once. This type of multi-gene panel testing allows patients to learn about multiple inherited mutations at once.
Once a mutation is identified in a family, it is common practice to test each blood relative for the one, known mutation in their family, known as “single site” testing. This has been a cost-effective method for testing patients for a known mutation in their family.
With single site testing it is important that clinicians evaluate both sides of each, individual patients family. Providers need to consider the possibility of the patient carrying another mutation from the opposite side of the family. Single-site testing may not be the only appropriate testing for relatives of those with a known genetic mutation. Panel testing may be recommended for family members, especially for “affected patients”, patients who have had cancer.
One major concern with panel testing is the complexity of results. For many genes, clear management guidelines are not outlined and risk reduction strategies are not established. An additional concern is “variants of uncertain significance”, or VUS. In most instances, this is when a rare mutation is identified and the impact or protein function is unknown. In these cases, more data is needed to classify these variants.
With these complexities, clinical management should be determined by the patient’s personal and family history. You should discuss your personal and family history with your personal health care provider or a certified genetic counselor.