BETA What is chromothripsis?

Chromosomes are the carriers of genetic information, DNA, ensuring that each new cell gets the right instructions during cell division. But sometimes things don't go as planned. Mistakes can occur, leading to mutations. Chromosomal mutations involve changes in the number or structure of chromosomes, which can have serious consequences. One dramatic example is chromothripsis, or chromosome shattering, a rare event where chromosomes break into many pieces and get stitched back together incorrectly. This chaotic process can activate cancer-causing genes, oncogenes, disable tumor suppressors, and drive cancer development, often signaling a poor prognosis. In this Health Tree University video, Dr. Mora dives into what chromothripsis means for patients with myeloma and why it matters. What is chromothripsis and how often is it seen in newly diagnosed myeloma patients? So this is not RNA-based, it's actually DNA-based. So RNA are the messengers going in the cells, which are very important, but they come from the DNA that is really where the tumor starts. So the tumor starts where something in the DNA breaks or goes wrong, and then these normal cells are not normal anymore. So one of these events that we believe can be early but also late, it's kind of heterogeneous in this timeline in the pathogenesis of myeloma, so from the first cells to the last, it's unclear, it can occur in different time points. But this is basically when one or two chromosomes, so more than two, at a certain point pulverized, they shatter. And so you should think, I have a puzzle, and it's already done, like 1,000 pieces, you've done it, you've spent a lot of time, all your 40 years lifespan, and at a certain point you just shatter the puzzle, and then there is a robot that tries, which is basically our self-control and self-mechanism of fixing things in our body, try to fix this puzzle. And it fixes because the cells survive, but it fixes in a wrong way. And so basically all these pieces are put together in a wrong way, and that creates multiple copy number loss, basically deletions, so you miss pieces, you have pieces that are duplicated, so think about you have a piece, another piece, you lose one, and you create duplication of this one to fill the hole, and also it basically creates a big mess. That's what chromotripsy means, it's basically messy genomes. And these events seem to be in 20-30% of new diodes, multiple myeloma patients, and seems to be associated with high-risk behavior in the VRD, the Nalidomide-Bortezomib combination therapies. We still have limited data on CAR-TB specific and daratumab or isatoxin-alanine-dissolidate antibodies. We're doing some studies, so hopefully soon we will provide some evidence, but in principle chromotripsy is this type of events, very complicated thing that can happen in myeloma, unfortunately. You need to do genome sequencing, not exome, not targeted. Whole genome sequencing is the only technology that can for certain give you this, identify these alterations. So that's why we like a lot whole genome sequencing, because we think that if the tumor starts from a DNA and then affect the RNA, you want to start from the alpha, the first alterations to understand all the rest, then DNA, then you add the RNA, you add the epigenetics, but I think DNA is really the core of our research right now, because we believe that it's the key to unlock the reason why myeloma happens and why myeloma behaves in a certain way is there. And of course it can express with changes in transcriptomic, epigenetic, there are a lot of people we're collaborating with that are very invested in those, so I'm not saying that those are not important, I'm just saying that those need to be connected with the DNA to really make a big step forward in research in myeloma.