Germline and somatic testing: what the difference is

Germline and somatic are just labels for when a gene change happened.

Germline changes were there from the start. You inherited them. They sit in nearly every cell of your body. That includes the cells in a saliva or blood sample.

Somatic changes showed up later. They arise in one line of cells during your life. They are found in a tumour and not in the rest of you.

Same word, "mutation". Completely different question being asked.

NCI defines the inherited kind this way. Genetic testing looks for specific inherited changes in a person's genes. Those changes are sometimes called mutations or pathogenic variants. They may increase the risk of diseases such as cancer.

Tumour testing has a different job. NCI says genetic testing of tumours is sometimes used to guide treatment. It looks for genetic changes that occurred during someone's lifetime.

NCI draws the line clearly. Genetic testing for inherited cancer risk is different from genetic testing of tumours. Tumour testing can sometimes detect inherited changes too. But it does not replace testing for inherited cancer risk.

That last point is the one people miss. Having your tumour profiled is not the same as being checked for an inherited risk.

For treatment, somatic results usually matter most. They show what is driving this tumour. They also show whether a drug exists that targets it.

For your family, germline results are the ones that travel. NCI makes the point plainly. Unlike most other medical tests, genetic tests can reveal information about the person tested and about that person's blood relatives. A positive germline result gives important information. It can help other family members make decisions about their own health care.

For your own future care, an inherited result can change things too. It can shift talks about surveillance and risk reduction. A tumour result does not do that.

It happens. A sequencing panel run on tumour tissue may flag a change. It may look inherited rather than acquired.

NCI's position on this is short. Tumour testing can sometimes detect inherited changes as well, but it does not replace testing for inherited cancer risk. The tumour test can raise the question. A dedicated test for inherited cancer risk is what answers it, so ask your team whether one is needed in your case.

Not every finding lands cleanly. NCI defines a variant of uncertain significance, or VUS. It is a genetic change for which there is not enough data to know whether it increases the cancer risk or not.

Two things follow from that.

First, a VUS is not a positive result. Do not treat it like one. Second, it is not permanent. NCI notes a VUS may be reclassified in the future as researchers learn more about these genetic changes. So NCI says it is important to keep in touch with the provider who performed the testing.

Put a reminder in your calendar. Nobody usually chases you about reclassification.

NCI says genetic counselling is generally recommended before any genetic testing for inherited cancer risk.

NCI describes what that session covers. It includes an assessment of how likely an inherited cause is. It covers whether testing is appropriate for you, and what the possible results would mean. It also covers the psychological considerations involved, and the specific tests being used.

Has nobody offered you that while inherited risk is on the table? It is entirely reasonable to ask for it. Are you unsure which test you have already had? Ask that too. It is a common point of confusion. The answer tells you what question you are still waiting on.