What are the different types of mutations in myeloma? For example, translocations, deletions, insertions, and amplifications. It's a complete arcane language, the description of the cytogenetics of multiple myeloma, but it's actually really, really simple. And so the simplistic approach is half of myelomas have a translocation, which is where two bits of DNA are joined together, they break, and then they move to different locations. And you move a super enhancer, which lands somewhere else and overexpresses a gene from that site. Straightforward. Hyperdeploytis is simply an extra copy of a whole chromosome, so they tend to be odd numbered chromosomes. And the most important one is gain of one Q and amplification of one Q. So that's copy number gain, translocations. And then there are these other structural abnormalities. So when you break apart, you can lose a bit of inflammation. That's called an interstitial deletion, and that can take away a gene totally. And then if you copy up a specific region, that's called an interstitial gain or amplification. And again, that can lead to overexpression of the gene. So I think that's most of the words that are used. Chromosomes do have a tendency to break and rejoin. Now, if I break chromosome one or chromosome four and rejoin it, no loss, nothing, no problem. We just broke it, rejoined it. And cells do a lot of that. They repair chromosomes all the time. But imagine if chromosome four breaks, and so does chromosome 14. It breaks. And then when they rejoin, they rejoin a piece of four with a piece of 14. They didn't join in the right combination, and you end up now with a chromosome that we refer to as a 414 translocation. So a chromosome translocation is the breakage and rejoining of chromosomes across their numbers, 414, 1114. Those are kind of things where chromosomes are breaking and rejoining. And the reason that that can be a problem is that it oftentimes starts putting genes together in novel combinations that now change how they function. And some of these chromosomes that rejoin are joining genes that aren't normally joined together, but when they are joined together, they take on new functions, like causing a cell to divide, for example. It turns out that we know that there are some chromosomal translocations that occur fairly commonly in myeloma. This slide that I'm showing here is called the circus plot. Not to be confused with the Ringling Circus, the circus plot here simply shows which chromosomes are joining together. You'll notice the circle has numbers on it. Those are all the 1 through 22 chromosomes. And you'll notice there's an example there where there's a pink bar that joins 14 and 11. And the width of that bar is a reflection of how many times we see it. 1114 is a relatively common translocation, whereas 1420, thinner bar in purple, is a little more rare. But every one of those chromosomal rejoins has been associated with data collection with changes in myeloma that may impact how aggressive that myeloma might be. Right now, at this point, just understanding chromosomal abnormalities gives us information about how aggressive a myeloma might be. In the table I'm showing on this slide here, a lot of words on it, but the simple point I wanted to make is that a lot of these chromosomal translocations not only give us an idea of how aggressive the myeloma might be, but it also gives us an idea of which therapies might be best for individual translocations. So the genetic information is giving us insight as to how aggressive the disease might be and which therapies might be useful. When we look at genes and cytogenetics in multiple myeloma and the chromosomes of the cancer cells, we try to look to see if there's any mutations. And there's different types of mutations that we can see in cancer. There's translocations, there's deletions, there's insertions, there's amplifications, and each one means something completely different. So let's start with defining each one of these. Deletion is where a section of the chromosome in that cancer cell is removed or lost, and it's disappeared completely. And whenever we say that, we normally refer to it as a deletion of the chromosome and a specific portion of the chromosome and the majority of the times. So a deletion of 13 chromosome or 13q deletion or deletion of 17p, those are just examples of deletions of parts of the chromosome that are related to multiple myeloma. Now, for example, in deletion 17p, we're talking specifically of a small portion of the chromosome number 17 that is part of the 23 chromosomes that are in pairs in the cancer cells. So for 13 deletion, the whole 13 chromosome is missing in the cancer cell. Sometimes you can have the whole chromosome missing, like 13 deletion, or you can have fragment of that chromosome missing, like the 13q deletion. There's other types of chromosomal mutations like translocations, and translocations is when a section of the chromosome is transferred to another chromosome within that same cell. So an example of that is, for example, translocation 1114 or translocation 414. That means that there's a portion of the chromosome 4 that moves to chromosome 14, and portion of the chromosome 14 that moves to chromosome 4. And they shouldn't be there in a normal cell. So that, for example, is a translocation 414. And just like that, there's several translocations in multiple myeloma that we look at that can help us establish whether a patient has high-risk disease and likely to relapse or if they have standard disease. Now there's other types of mutations like duplications. And basically what that means is that a part of a section of a chromosome breaks off and has more pieces added to that same part. So it's basically reproducing or replaying the same gene within a chromosome. And that causes extragenetic material in the gene and in the abnormal cell. There's also insertions where there's a portion of a gene that was either floating around or that came from a virus or from a foreign portion or within the same genome of the human cell that actually gets inserted into a chromosome without actually having it being replaced with another, like the translocations. And the insertion, instead of switching places, is just basically adding one extra gene or portion of the chromosome to an existing chromosome. Inversion is another type of mutation that we see where a part of the gene within the chromosome breaks off, flips, and then gets fused back into the chromosome. So basically the material that it contains is all inverted. And it's as if we were reading backwards the recipe of how the cell should grow and how it should behave. So those are the most common types of chromosomal mutations. In multiple myeloma, the most common ones I would say are deletions, translocations. We also see an excess amount of chromosomes, hyperdeployed as we use it in medical terms. Or a loss of the complete chromosome, which we also call hypodeployed, or a lower amount of chromosomes than the normal 46 chromosomes that we have.