Can only one allele of chromosome 17 have a deletion? How does this affect risk?

[Music] can the gene p53 found on the p arm of chromosome 17 be mutated in one allele and deleted in the other allele absolutely and it becomes even more complicated if you think if you go back to what we said before and you realize that any of these mechanisms could happen in a percentage of cells but not in you know the cell next door so it's it's becoming very complicated but i think eventually this is one of the unmet needs in myeloma we are already becoming sophisticated but even more the really declaring the status of p53 each and every patient because we know how important it is for normal plasma cells who know how important it is for risk prognostication for our patients clearly p53 myeloma in our clinics is a very difficult disease to treat and these patients are at particular risk of faring poorly down the line this is one of our utmost priorities at this point how to tackle this particular any high-risk myeloma of course but within the category of high-risk myeloma p53 mutated myeloma seems to be on the ultra-high risk end of the spectrum so we're very interested in in the lab we are focusing on how to generate novel models of p53 mutated myeloma so we know which therapies both established and experimental these cells may respond to and bring those to the clinic can only one allele of chromosome 17 have a deletion how does this affect risk when we're dealing with when we're looking at chromosome mutations there's a lot of information that we need to know so when we talk about 17p in particular i want to go back to what a chromosome looks like i want you to to think of the of a chromosome as looking like an x with the two top uh portions being arms being smaller than the lower portions and those top portions are what's called p and the lower portions is what's called q so whenever somebody has a 17p deletion it means that it it is missing one of those small arms in the x chromosome or in the chromosome that forms the x specifically of chromosome 17. and why is it important to for for us to know um if somebody has a 17p deletion or why do we see that this mutation is so high risk in people with multiple myeloma in this portion of the chromosome there is a gene called tp53 and tp53 is the gene that actually helps modulate the cell and determines when the cell can replicate when the cells should shut down when there is damage to the cell and it needs to break and repair and it is a very important gene to prevent cancer when you're missing the 17p chromosome the gene of tp53 could go away with it and if you have less of that gene that helps regulate the cell and tells the cell to die if there's an abnormality in the cell or to fix whatever damage it has or to halt its cycle or to speed up its cycle then that prevents the myeloma the myeloma cell or cancer cells in general from dying so if you're missing just one allele of the tp53 versus missing both of them in the chromosome you're going to see a difference in how aggressive the cancer cell can can survive and how it can proliferate if you have nothing that's telling controlling how fast the cell lives by missing both alleles then there's a likelihood that the cancer cell has a ability to proliferate and survive more than if you have one of those genes that helps prevent that or if you have both of those genes intact so whenever we're talking about 17p deletion it's important to know it does make a difference if if both alleles are affected or if only one allele is affected and then it's also important to know what percentage of all the cells are affected as well because as we said the more cells that are affected the more likely that the myeloma is going to behave very aggressively but also if we see that more alleles or less control of the cancer cell is available then there's a higher chance that that cancer is going to grow fast and proliferate so to kind of recap when you have a chromosome that's missing if that portion of the chromosome knocks out a gene that helps regulate the cell and prevents it from proliferating if it's abnormal if you have the two genes that help control that not functioning it's much worse than if you have one of those genes functioning and the other one not functioning and it's also worse than if you had both genes functioning so you ideally want to have the two genes functioning so they can regulate the mutated cells and then if that's not the case you would like to have at least the function of one of the genes so that it can kind of slow or control to some extent as opposed to having none of those genes regulating how those cells are going to proliferate and it's going to make the cancer cells survive longer