In the Basic Cancer Genetics and Tumor Biology course, we explored the key differences between germline and somatic mutations. Germline mutations are inherited—they’re found in reproductive cells and can be passed on to children. Somatic mutations, on the other hand, occur in non-reproductive cells and are not inherited. These changes only impact the individual in whom they occur.
Understanding this distinction is especially important when we talk about genetic testing in multiple myeloma. It helps explain how this type of testing differs from something like a BRCA test, which looks for inherited mutations that increase the risk of certain cancers.
In this video, our expert doctors will break down these differences even further and explain what they mean for your care and treatment decisions.
How does the genetic testing done in myeloma differ from BRCA testing for breast cancer or consumer DNA tests like 23andMe?
BRCA is testing for the risk of familial breast cancer. And that looks more at what we call a germline mutation within the patient. So these are mutations that you have had from birth. And those predispose the patient to getting, in this case, breast cancer or ovarian cancer. So it is more looking at familial risk of getting breast cancer rather than just what is the genetic makeup of the cancer itself.
When we talk about genetic testing in myeloma, we're looking for the genetic makeup of the myeloma cells themselves. It is not so much to do with the genetic makeup of the patient, but more about what mutations within the cancer cell are driving these mutations. So we call them somatic mutations. And these are different than germline mutations.
If you were to take a healthy cell out of that patient, like a cheek swab, and you were to look at the genetic makeup of that cell versus the genetic makeup of the cancer cell, which is a myeloma cell, it would be very different. These are the mutations that have been acquired along the way that have caused those cells to become cancerous.
Why is genetic testing done?
They can provide different pieces of information for a myeloma patient. The first and foremost is prognostication. There are certain genetic mutations out there, like deletion of 17p, translocation 4;14, and gain 1q, that are associated with worse prognosis. So for those patients, therapy tends to be a little bit more aggressive, and we need to be following them more closely.
It can also provide data that can help guide therapy. Based on different trials, data suggests that certain types of therapy work better with certain mutational signals, and that can lead to better treatment guidance.
There have also been multiple attempts to find specific molecules that can target specific mutations. There is some data about what we call familial multiple myeloma, whereby there are certain families that have a higher risk. However, the data is not as robust as it is for breast cancer. More research is needed to help determine whether people in certain families have a higher risk of multiple myeloma.
One of the biggest differences is the chromosome changes. The mutations that we see in the myeloma cells are typically something that the cell or patient has acquired over the years in that particular plasma cell. It’s not something that they are born with or can pass to their children.
For example, the BRCA gene in breast cancer is something someone is born with and may pass on to their offspring. But plasma cell mutations that we see in myeloma are acquired during a patient’s lifetime and are only in the malignant plasma cells, not in their normal healthy cells.
Right now, we don't have any predictive genetic testing to say someone is going to develop myeloma or that their children will. There’s not a specific mutation test like that.
Consumer tests like 23andMe study the genetics of the body and DNA that make up you as a person. That’s not what we mean in terms of myeloma. Cancer is a genetic disease, and the genetics of cancer involve abnormalities such as mutations and chromosomal translocations.
Genes may become inactivated or overactivated, and we’re still learning about epigenetics. Cancer cells have gone wrong—but that also gives us an opportunity. Since cancer cells have mutations, there are features that can be targeted by therapy.
If we can switch off the signals that keep the abnormal cells alive, they can die naturally. A good example of that is targeting the BCL2 gene with venetoclax. The 11;14 subset of myeloma is very sensitive to that drug—it commits suicide and dies.
So it’s really important to study the genetics because it can help us find new treatments, predict response to therapies, and predict risk for each person. Understanding these genetic details may hold the key to curing people.
To better understand the differences between somatic and germline mutations mentioned earlier, watch the HealthTree University lesson on this topic in our Basic Genetics and Tumor Biology course.
What is cytogenetics?
Cytogenetics is the study of chromosomes, which are long strands of DNA. This DNA makes up the majority of the genetic information that cells have. When we study cytogenetics, we try to understand if there are any changes in the chromosomes—such as breaks or fusions—that help us understand what abnormalities are seen in these cells.
In simple terms, we have a “recipe book” in our cells, and that recipe book is DNA. It contains all the instructions for how our cells function and how our body behaves. Chromosomes store this DNA information in strands. Humans have 46 chromosomes in each cell, which contain all the DNA content that helps us survive.
How is cytogenetic testing done?
Cytogenetics can be done using different technologies. You could do karyotyping, banding studies, or fluorescent in situ hybridization (FISH). You might hear this word often when talking with your doctor.
Cytogenetic studies can be done on any type of cell, but when dealing with cancer—especially multiple myeloma—we focus on the cytogenetics of the cancer cells or myeloma cells. By studying these, we can better understand what characteristics the cancer cells have and whether there are mutations that make them more aggressive or resistant to treatment.
Nowadays, as targeted therapy becomes more common, cytogenetic testing helps identify mutations that can be targeted with specific drugs.
Cytogenetics basically means testing the chromosomes of the cell, and that can be done in different ways. One traditional way is karyotype analysis—looking at the structure of the chromosomes in dividing cells. However, this often doesn’t work well in multiple myeloma because most cells won’t divide outside the body.
That’s why we rely on a technique called FISH (fluorescence in situ hybridization). In multiple myeloma, FISH uses colored probes to mark chromosomes and identify deletions or translocations.
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