What are the different types of chromosomal mutations?

In previous Health Tree University lessons, we explored how gene mutations are classified. Now let's zoom out and focus on the bigger picture, the chromosome. In this lesson, we'll dive into the different types of chromosomal mutations and how they can impact our DNA. Get ready to unravel the next layer of genetic changes. What are the different types of chromosomal mutations? 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 has different, means something completely different. So let's start with defining each one of these. So 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 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 the chromosome breaks off and starts to 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 extra genetic 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, it's just basically adding one extra gene or portion of the chromosome to an existing chromosome. And 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. And 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. Some of the abnormalities may be chromosomes break and rejoin in unusual ways. Let me show you some examples of that. Here's an example of a term you may have heard in myeloma called hyperdiploidy. Hyperdiploidy simply means that you have more copies of chromosomes than you would expect simply with a pair from mom and dad. Think about the fact that every time the sperm and the egg get together and form an individual, that sperm and egg now have to divide to form all the tissues of your body. So what arose from a single pairing of two cells now is being divided into trillions of cells that make up your body. And every time those cells divide, they have to copy their DNA and pass it on to the next cell. Copy the DNA, pass it on to the next cell, and organize those into chromosomes so that every cell gets its due share of pairs of chromosomes. Sometimes mistakes are made. And in myeloma we're finding that chromosomes can be very abnormal in myeloma, generating what we refer to as hyperdiploidy. And as you see in this slide, that one of these myelomas on the right has three copies of chromosome 1, three copies of chromosome 3, three copies of chromosome 9 and 11 and 15. There are a lot of chromosomes in this myeloma cell. So one of the hallmarks of myeloma is the identification of these chromosomal abnormalities. Some of these abnormalities actually are associated with more aggressive disease. So already looking at chromosomes, we can learn a little bit about how aggressive this myeloma might be. The other possibility is, chromosomes do have a tendency to break and rejoin. Now if I break chromosome 1 or chromosome 4 and rejoin it, no loss, no problem, we just broke it and rejoined it. And cells do a lot of that. They repair chromosomes all the time. But imagine if chromosome 4 breaks, and so does chromosome 14. It breaks. And then when they rejoin, they rejoin a piece of 4 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. So right now, at this point, just understanding chromosomal abnormalities gives us information about how aggressive a myeloma might be. And 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. 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.