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Mini genetic mystery: hereditary or tumor BRCA2 result? 3 clues to help decipher

During his routine physical exam, a patient informs you that his brother, who has prostate cancer, recently tested positive for a BRCA2 mutation. Your patient hands you his brother’s report and, at first glance, you agree that indeed his brother has a BRCA2 variant. You begin to consent your patient for genetic testing. But wait. Look again. Does his brother really have an inherited BRCA2 variant? Is genetic testing appropriate for your patient?

Hereditary genetic test results provide information about future cancer risk development; however, tumor genetic test results provide information to help guide cancer treatment. Therefore, it is imperative to know the difference. Here are three ways to determine whether you are looking at a hereditary (germline) genetic test result or a tumor (somatic) genetic test result.

Clue #1:  Specimen type

The specimen type is most often located at the top of the report near the patient demographics. This will tell you what biological material was sequenced. If it is listed as tumor tissue from the prostate, uterus, pancreas, or other solid tumor site, then you know right off the bat that the sequencing was done on tumor (cancer) DNA. Testing of a person’s cancer is called somatic testing. Somatic variants develop spontaneously over an individual’s lifetime and are not passed from generation to generation. Hereditary genetic test reports, on the other hand, most commonly have the specimen type listed as blood, saliva, or buccal. These sample types are representative of the individual’s entire germline; the hereditary genetic material you are born with and will pass on.

Clue #2:  Diagnosis

You are likely looking at a tumor genetic test report if a patient’s known or suspected cancer diagnosis is listed at the top of the actual result. Whether it is pancreatic adenocarcinoma, invasive ductal carcinoma, or lung cancer, the purpose of this testing is to determine the most effective cancer-specific treatment options for each patient. You will often see lists of FDA-approved therapies specific to the patient’s tumor type. You may also see select clinical trials matched for the patient’s variant and disease. In contrast, a hereditary genetic test report is, for the most part, independent of the patient’s diagnosis. Hereditary reports usually provide details about future cancer risks and implications for family members. In fact, a person does not even have to have cancer or even family history of cancer to pursue hereditary cancer testing.

Clue #3:  The gene list

Ok, so this one isn’t as helpful per se. Many tumor and germline genetic test reports have identical or near-identical gene lists. So, the gene list itself may not be the clue you need. However, it is important to know that they can be the same, so that when you see familiar genes like BRCA1, BRCA2, TP53, and MLH1, you know to keep looking for clues.

Alas, your sleuthing has worked! You determine that your patient’s brother’s report is actually a sequencing analysis of his tumor, rather than his germline. Your patient calls his brother and finds out that his subsequent hereditary genetic testing was negative. You review the rest of his family history and determine that your patient does not have a higher-than-average risk to have a BRCA2 variant and testing is not indicated.

These are quick clues, but the Quest genetic counselors and laboratory directors have years of experience in both somatic and germline cancer genetics and can help interpret test results and make test recommendations. They can be reached at 1.866.GENE.INFO (1.866.436.3463) or