If deletion 17 p is not detected at diagnosis, can it develop later in myeloma?

In this Health Tree University lesson, we break down how the 17p deletion, a high-risk genetic mutation in multiple myeloma, can develop or expand over time, even if it wasn't detected at diagnosis. You'll learn how clonal evolution works, how the percentage of myeloma cells with this deletion can increase, and why ongoing monitoring with FISH or next-gen sequencing matters. If you did not have the deletion of 17p at diagnosis, could you acquire this mutation later in your disease? That's actually something that's pretty commonly seen. I mean, sometimes we see 17p deletion at the initial diagnosis, but more frequently we'll see it later on, like when there's a relapse of myeloma and we're repeating a bone marrow biopsy, we'll see what we call an acquired 17p deletion. Now, it's hard to know if it's something that occurred just as a myeloma has evolved, or if it was there before at a super low level that has now grown over time. But it is something that's commonly seen, particularly as myeloma relapses, and particularly with later relapses. Now, in terms of evolution, yes, you can have 17p evolve. So somebody may not have had it at newly diagnosed state, but with relapses after other therapies, you can bring out a clone that might have this abnormality. So it's another one of those things that you have to look for. And these types of changes are one of the reasons patients, especially if the clinical behavior of the patient doesn't match what you expect, it's worth going back to the biopsy, right? Because let's say the problem with an initial diagnosis is we're asking for a crystal ball. Let's look at your ISS stage and your genetics and let's see what happens. But you know what's more important than the crystal ball is what actually happens, right? So if the remissions are shorter than you would have expected, it's worth going back to see if perhaps these other mutations or abnormalities have developed since the initial diagnosis. Well, something's changed in the myeloma as it's been exposed to certain medications, or just as it's been present for a long period of time. It's one of the ways that the myeloma has figured out how to survive and grow. And unfortunately, when we see 17P deletion, it can be associated with more aggressive relapses, for instance, maybe more rapid relapses or relapses in unusual locations like extramedullary sites. And typically does because it's the like if you think about a bunch of different clones in the patient, the ones that we have more trouble getting rid of and keeping away are usually the high risk. So it wouldn't be uncommon to see the 17P deletion, for example, increase in the number of cells as patients relapse over time. Can 17P deletion be present at diagnosis and not reported on your FISH report? So when cytogenetics are being reported, again, we earlier talked about there's a karyotype part and a FISH part. So now the FISH uses probes to understand whether there are certain mutations present. The probes will go and query all the cells within and only if a mutation is present above the limit of detection of that particular probe of that particular lab will the test be positive, meaning you look under the microscope, you see it shining and you know that mutation is present. But imagine, you know, there are changes. There is a deletion, for example, 17P present, but it's less than 1%. And the limit of detection of the test is 2%. That will not be reported, you know, because the test is just not sensitive enough to pick that 1%. And what may happen is that we treat this patient's newly diagnosed myeloma. And eventually when relapse happens, this 1% that stays hidden or rather it was not reported, that may be the clone that evolves into the relapsed myeloma and that at the time of relapse may present itself as 10%, 20%. So it's the selective multiplication of that clone that may happen. So yes, it is quite possible that initial FISH reporting at the time of diagnosis may not pick up all translocations or mutations because it may be below the limit of detection of that particular test, which behooves the point that, you know, there has to be newer technologies that are able to capture mutations and translocations at the least amount of detection possible or what we call as the limit of threshold should be much, much lower for detection so that we are able to capture even the presence of that translocation or a mutation to keep an eye on things.