What types of chromosomal mutations are present at diagnosis? (early events) What types of chromosomal mutations can be acquired over time? (later events)

In a previous Health Tree University lesson, we explored the different types of chromosomal abnormalities that can occur in cancer. In this lesson, we'll take it a step further, discovering which mutations are present at diagnosis and which ones can develop over time. Understanding these changes is key to making informed decisions about treatment and disease monitoring. What types of chromosomal mutations are present at diagnosis? What types of genetic mutations can be acquired over time? There are separate events that occur in the development of multiple myeloma. They're the ones that we call primary genetic events or things that really seem to be the initiating event, the thing that leads to the myeloma cell becoming cancerous. And there are ones that can be picked up over time. Classically, we think of some of what we call the translocations, where the one chunk of the chromosome is moved to another chromosome and basically it puts a gas pedal to the floor on something that causes the cell to go into overdrive. It shifts its gears into high gear. What are some of the translocations that are considered primary events? Some of the translocations that tend to be more primary events are 11-14 translocation, 4-14 translocation, 14-16 translocation, 14-20 translocation. These are some of the things we think of as being initiating events in multiple myeloma. If you don't have a translocation at diagnosis, can you acquire it later? Generally no. We think of those as ones occurring at the beginning and translocations are not something that people acquire later at a later time point in their same myeloma clones. In rare cases, a translocation may be present at diagnosis but not detected by FISH testing. This can occur if the bone marrow sample is not collected or prepared properly. Additionally, FISH usually relies on analyzing a limited number of cells and if the translocation is present in only a small fraction of cells, it may be missed. For this reason, FISH panels should include the translocation probes that relapse. What chromosomal mutations can be picked up over time? Larger genetic events that affect chromosomes that can be picked up over time are 17P deletion, 1Q gain and 1P loss. Those things are changes that occur anytime in the myeloma disease course. Same with actual mutations to P53, those can occur later on as well. They don't necessarily initiate the development of myeloma but can change the trajectory of myeloma over time. It's important to note that 17P deletion and chromosome 1 abnormalities can be present at diagnosis. While they are not considered initiating events, they may develop early in the disease for some individuals. Since these abnormalities can also emerge later in the disease course, FISH testing with these probes is recommended at disease relapse to monitor for their presence. Understanding the genetics of your myeloma is crucial. Knowing your risk status can help guide your decisions about treatment and maintenance therapy and it may also reveal a targetable mutation. To track your genetic profile, sign up for Health Tree Cure Hub. Once your medical records are connected, you can view your genetic profile by clicking the Track My Disease button on your dashboard. The Health Tree Cure Hub AI algorithm will then use this information to suggest treatment options and relevant clinical trials.