When you’re diagnosed with multiple myeloma, you’ll likely hear your care team talk about genes, mutations, and chromosomal changes. This can be a complex topic, but having an overview of what these terms mean can help you better understand your treatment options and have deeper discussions with your care team.
Keep reading for a simple guide on why testing is a critical piece of your treatment plan.
How genetic testing is done
When we talk about genetic testing, we’re talking about two different types:
- Germline testing, or the genetics you’re born with. Most individuals with multiple myeloma don’t have a family history of the disease, but if you do, your provider may order a genetic test (done using a blood sample) to better understand any implications for family members.
- Biomarker or genomic testing, which accounts for the genetics of the tumor. In multiple myeloma, this testing reveals mutations in genes that drive growth and survival. It helps explain the behavior of the cells, resistance to treatment, and identifies targeted options
Genetic testing in multiple myeloma is typically done with a bone marrow biopsy or a liquid blood-based biopsy. The sample is then analyzed using specialized tests such as:
- FISH (fluorescence in situ hybridization): Detects chromosomal changes like translocations and deletions
- Cytogenetics: Looks at the number and structure of chromosomes
- Next-generation sequencing (NGS): Identifies mutations in specific genes such as KRAS, NRAS, BRAF, TP53, and others
These tests help your care team understand whether your risk level is standard or high and can help determine which treatments may be most effective for your cancer.
Why genetics matter in multiple myeloma
Multiple myeloma is not one single disease. It develops in different ways depending on your specific genetic changes. These genetic changes can affect how fast the cancer grows, how it responds to medications, and your long-term outlook.
That’s why having a closer look at your genetics plays a major role in building a personalized treatment plan.
RAS pathway genes (KRAS, NRAS, BRAF)
More than 50% of patients with multiple myeloma have some sort of RAS mutation. These are genes that regulate cell growth and can be detected through a liquid or bone marrow biopsy. When they’re mutated, they can make cancer cells grow more quickly. Certain targeted therapies may work better for patients with a specific RAS pathway mutation.
Tumor suppressor genes (TP53)
TP53 is a gene that controls the rate of cell growth and death and helps keep damaged cells from multiplying. When TP53 is lost or mutated, cancer cells can grow unchecked. TP53 mutations or deletions (often seen as del(17p) on FISH testing) are considered high-risk. Although TP53 deletion isn’t common in recently diagnosed patients, it’s seen in up to one in cases in patients with advanced-stage disease. Patients with TP53 changes often need more aggressive approaches because treatment resistance is likely.
Other important genetic changes
Researchers have identified additional genes frequently involved in multiple myeloma. Chromosomal translocations happen when pieces of two different chromosomes swap places. In multiple myeloma, this can turn on certain cancer-related genes, giving myeloma cells a growth advantage.
The most common translocations involve a gene called IGH on chromosome 14. These are primary changes, meaning they usually happen early in the disease, and are found in about half of patients. They often involve genes like CCND1, CCND3, FGFR3/NSD2, MAF, and MAFB, which can become overactive when moved next to the IGH enhancer. One specific translocation, t(4;14), can affect two genes at once.
Other changes, like rearrangements of the MYC gene, usually appear later. MYC changes happen in roughly 15–20% of newly diagnosed patients and can make the cancer grow faster.
How this information guides treatment
Your genetic testing results help your care team understand how your myeloma is likely to behave and which treatments may work best. Some mutations respond better to certain drugs or targeted therapies, while high-risk changes may mean you need a more closely monitored treatment plan.
These results can also help identify clinical trials that are a good match for your specific genetic profile. Overall, your genetics allow your doctor to personalize your care so you receive the most effective treatment for your type of myeloma.
If you haven’t discussed your genetic testing results yet, ask your doctor about your FISH, cytogenetics, or NGS findings. These conversations can empower you to take an active role in your treatment plan.
As always, if you would like to connect with an Outcomes4Me oncology nurse practitioner at no charge through the Outcomes4Me app, just use the “Ask Outcomes4Me” button.
