Approximately 10 to 15 percent of childhood cancer cases are due to a genetic predisposition. Children’s Mercy Kansas City is searching within the genetic code to not only identify genes that may lead to cancer, but to find answers in how to better treat or cure pediatric cancer.
Erin Guest, MD, Director of Cancer Genomics at Children’s Mercy, discusses the growing role of cancer genomics and how big data, new tests, and personalized treatments could change the future of pediatric cancer treatment.
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Cancer Genomics: Finding Answers Through Data and DNA
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Learn more about Erin Guest, MD
Erin Guest, MD
Erin Guest, MD, is a pediatric hematologist/oncologist and Director of the Cancer Genomics Program and Cancer Center Biorepository at Children’s Mercy Kansas City. She is also Associate Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine. Dr. Guest received her medical degree from the University of Oklahoma College of Medicine and completed her residency in pediatrics at Children’s Mercy Kansas City. She is fellowship trained in pediatric hematology/oncology from Children’s Mercy Kansas City.Learn more about Erin Guest, MD
Transcription:
Cancer Genomics: Finding Answers Through Data and DNA
Dr. Mike Smith (Host): Our topic today, is Cancer Genomics, Finding Answers Through Data and DNA. My guest today, is Dr. Erin Guest. Dr. Guest is a Pediatric Hematologist/Oncologist and Director of the Cancer Genomics Program and Cancer Center Biorepository at Children’s Mercy Kansas City. Dr. Guest, welcome to the show.
Dr. Erin Guest (Guest): Thank you, so much. Glad to be here.
Dr. Smith: Let’s just maybe step back for a moment because so much is happening in the field of genomics – especially cancer genomics. You as an expert, I kind of just want to get a nice summary – where do we stand today, really in understanding genomics and pediatric cancer?
Dr. Guest: We’ve come a long way in the past five years. It’s a really exciting field because it’s really helping us to understand not just how to better treat the disease, but really how to better categorize. We can take genomic information, and we can make subcategories of diseases that previously were described by the way they look under the microscope or some other individual genes that might be mutated in cancer. Now, we can learn so much more about the origin of where cancer may have come from, and in some cases, we can help families understand why their child developed cancer in the first place. That’s another really important aspect of pediatric cancer, especially when most of these diseases are not being caused – are potentially being caused by genetic changes rather than environmental influences.
Dr. Smith: Yeah, so, Dr. Guest, you alluded to this. Obviously, genomics is a huge field, right? [LAUGHING] I mean, there are so many different things to study. What exactly is the focus at Children’s Mercy, and what are you hoping to accomplish?
Dr. Guest: We’re really fortunate at Children’s Mercy. We have a Center for Pediatric Genomic Medicine where we have the latest, state-of-the-art sequencing equipment. We have our own, in-house pipeline informaticist; we have a molecular oncologist who is helping us with this type of work. Our focus has been on helping with diagnostics, like we mentioned, helping to determine what might have caused cancer in a patient if they might have a predisposition syndrome, but then taking a really well-rounded look at the cancers, not just looking at the DNA in cancer itself – the DNA is just the tip of the iceberg.
We’re interested in of course what those genetic mutations are, but we can use sequencing technology now to look at the RNA, which is what’s being expressed by the cells, and then what’s being translated then into protein within the cells. That kind of helps us really figure out what makes a cancer cell tick. And then, we can also use some of the really, really cool, new technology, the single-cell sequencing, where we can look at just one individual cell. We can see what the mutations are in the cell, and how that cell is functioning, and what RNA is being expressed.
We can look across an entire tumor, and it’s really interesting that not every single cancer cell in one tumor is identical to each other. In a patient that has a tumor with metastatic disease, the original tumor and the metastatic disease may be different, and we can use that single-cell technology to really hone in on how has cancer changed over time? How is it using genetic mutations and changes to get around the treatment that we’re providing, and then how can we use that to our advantage to improve our treatment?
Dr. Smith: The whole thing that’s so fascinating to me, Dr. Guest, is the idea – this cancer has a certain genetic code, but then understanding what influences the expression of some of these cancer genes and some of these mutations. That could be very powerful, right? That’s I think what people refer to as the epigenetics – the above the gene influences on the expression of these mutations. What do you think about that? That, to me seems like such a powerful thing to be studying.
Dr. Guest: Right, exactly. Our new genome center director, Dr. Tomi Pastinen, comes to us with a background in epigenetics, so we’ve really been able to incorporate that into our cancer research as well. I think that’s going to really influence how we think of cancers. A cancer may or may not have a genetic mutation, but if there are changes in the methylation markers on the DNA, that can also change how the DNA is expressed. We can no longer just think of it as mutations in isolation. If we do that, then we’d miss a lot of that information that helps us understand what genes are turned off, what genes are turned on, how is that changing over time, how does that change as a result of treatment? Or, as that cancer learns how to work its way around a treatment, especially if it’s not responding very well, those methylation markers are really important.
We can look at those in our lab. The way that we do that is a methodology called Whole-Genome Bisulfite Sequencing, where we can look at the entire genome; we can look at those methylation markers that are attached to that DNA. That’s another area of brand new technology and research that I think is going to impact how we actually treat cancer very very soon.
Dr. Smith: Right, and stay ahead of that cancer during that treatment as well, right? As you mentioned, the cancers are able to resist some of that treatment as they start to learn how to get around that. By understanding the genetics and the epigenetics, Dr. Guest, you’re kind of staying ahead of that a little bit, and you can anticipate what some of these cancers might do and be ready to offer up a different type of treatment. It really is fascinating. I think a lot of physicians today – and I think a lot of lay people today – still think of the cancer genomics as something in the future. There definitely is still a lot of research we still need to do, and we understand that, but aren’t there things going on right now, today, in cancer genomics, that are helping patients live longer?
Dr. Guest: Sure. And we are using the technology to reclassify diseases. We can do – for example, we can do testing for a gene called BRAF, B-R-A-F. If we find a mutation in that gene, that can actually change how we might approach the treatment for that patient. That’s a test that we regularly do in our lab. And there are a lot of other examples of tests like that. We have really felt like it’s not – we can’t just focus on the genes that are known because there are going to be so many more things out there to discover that are going to impact how we think about cancer and treat it.
What we’re doing at Children’s Mercy, is doing clinical testing, but at the same time, using research funding. We’re very blessed to have research funding from a lot of different community organizations from Black and Veatch, from Big Slick, from Children’s Mercy Cancer Center, and now, our new Children’s Research Institute. All of these funds, we’re putting them towards being able to do innovative research investigations for all of our patients with newly diagnosed cancer and with relapses so we can start to put all of the pieces of the puzzle together. All of that research in combination with research being done around the country and around the world is really going to help us advance the treatment for all children with cancer.
Dr. Smith: It does. To me, it seems that Children’s Mercy is really in a great position to be a leader and an innovator in cancer genomics. I think that’s very exciting for Children’s Mercy. Where do you see all of this going? It’s a fascinating field; it’s a big field. We’ve touched on just a little bit of it. What excites you most about this, and where do you see this going?
Dr. Guest: I think the things that really get me excited are particularly the single-cell sequencing and then looking at the RNA, those newer technologies that are going to go beyond just what the mutations are – and the methylation, as well. I think that – I imagine that in another five years, we’re going to be doing clinical testing that’s going to focus on looking at individual cancer cells. Right now, when we take a look at a tumor -- at least the standard way of doing that is to mash up all of those tumor cells, take all of the DNA out of all of the tumor cells all at once. If we can really understand what’s going on in each cell and how that changes over the course of months for a patients cancer, and if we can get down to the single-cell level where we can just do a blood test, and be able to – maybe a patient has a tumor in their leg bone, but if we can draw their blood and find the information that we need out of that test on an individual cell level, that’s going to cut back on a lot of invasive type procedures for patients and make sure a huge difference for their care.
Dr. Smith: Fascinating, yes. Wow, just such an exciting field. Dr. Guest, I think you’re just going to have to come on the show occasionally, right and give us an update of where everything is at and where we’re going because it really is such a huge field. I know that Children’s Mercy is a leader, there’s so much research going on, and I’m excited for you. I also just want to thank you for coming on the show, today.
You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to ChildrensMercy.org, that’s ChildrensMercy.org. I’m Dr. Mike Smith. Thanks for listening.
Cancer Genomics: Finding Answers Through Data and DNA
Dr. Mike Smith (Host): Our topic today, is Cancer Genomics, Finding Answers Through Data and DNA. My guest today, is Dr. Erin Guest. Dr. Guest is a Pediatric Hematologist/Oncologist and Director of the Cancer Genomics Program and Cancer Center Biorepository at Children’s Mercy Kansas City. Dr. Guest, welcome to the show.
Dr. Erin Guest (Guest): Thank you, so much. Glad to be here.
Dr. Smith: Let’s just maybe step back for a moment because so much is happening in the field of genomics – especially cancer genomics. You as an expert, I kind of just want to get a nice summary – where do we stand today, really in understanding genomics and pediatric cancer?
Dr. Guest: We’ve come a long way in the past five years. It’s a really exciting field because it’s really helping us to understand not just how to better treat the disease, but really how to better categorize. We can take genomic information, and we can make subcategories of diseases that previously were described by the way they look under the microscope or some other individual genes that might be mutated in cancer. Now, we can learn so much more about the origin of where cancer may have come from, and in some cases, we can help families understand why their child developed cancer in the first place. That’s another really important aspect of pediatric cancer, especially when most of these diseases are not being caused – are potentially being caused by genetic changes rather than environmental influences.
Dr. Smith: Yeah, so, Dr. Guest, you alluded to this. Obviously, genomics is a huge field, right? [LAUGHING] I mean, there are so many different things to study. What exactly is the focus at Children’s Mercy, and what are you hoping to accomplish?
Dr. Guest: We’re really fortunate at Children’s Mercy. We have a Center for Pediatric Genomic Medicine where we have the latest, state-of-the-art sequencing equipment. We have our own, in-house pipeline informaticist; we have a molecular oncologist who is helping us with this type of work. Our focus has been on helping with diagnostics, like we mentioned, helping to determine what might have caused cancer in a patient if they might have a predisposition syndrome, but then taking a really well-rounded look at the cancers, not just looking at the DNA in cancer itself – the DNA is just the tip of the iceberg.
We’re interested in of course what those genetic mutations are, but we can use sequencing technology now to look at the RNA, which is what’s being expressed by the cells, and then what’s being translated then into protein within the cells. That kind of helps us really figure out what makes a cancer cell tick. And then, we can also use some of the really, really cool, new technology, the single-cell sequencing, where we can look at just one individual cell. We can see what the mutations are in the cell, and how that cell is functioning, and what RNA is being expressed.
We can look across an entire tumor, and it’s really interesting that not every single cancer cell in one tumor is identical to each other. In a patient that has a tumor with metastatic disease, the original tumor and the metastatic disease may be different, and we can use that single-cell technology to really hone in on how has cancer changed over time? How is it using genetic mutations and changes to get around the treatment that we’re providing, and then how can we use that to our advantage to improve our treatment?
Dr. Smith: The whole thing that’s so fascinating to me, Dr. Guest, is the idea – this cancer has a certain genetic code, but then understanding what influences the expression of some of these cancer genes and some of these mutations. That could be very powerful, right? That’s I think what people refer to as the epigenetics – the above the gene influences on the expression of these mutations. What do you think about that? That, to me seems like such a powerful thing to be studying.
Dr. Guest: Right, exactly. Our new genome center director, Dr. Tomi Pastinen, comes to us with a background in epigenetics, so we’ve really been able to incorporate that into our cancer research as well. I think that’s going to really influence how we think of cancers. A cancer may or may not have a genetic mutation, but if there are changes in the methylation markers on the DNA, that can also change how the DNA is expressed. We can no longer just think of it as mutations in isolation. If we do that, then we’d miss a lot of that information that helps us understand what genes are turned off, what genes are turned on, how is that changing over time, how does that change as a result of treatment? Or, as that cancer learns how to work its way around a treatment, especially if it’s not responding very well, those methylation markers are really important.
We can look at those in our lab. The way that we do that is a methodology called Whole-Genome Bisulfite Sequencing, where we can look at the entire genome; we can look at those methylation markers that are attached to that DNA. That’s another area of brand new technology and research that I think is going to impact how we actually treat cancer very very soon.
Dr. Smith: Right, and stay ahead of that cancer during that treatment as well, right? As you mentioned, the cancers are able to resist some of that treatment as they start to learn how to get around that. By understanding the genetics and the epigenetics, Dr. Guest, you’re kind of staying ahead of that a little bit, and you can anticipate what some of these cancers might do and be ready to offer up a different type of treatment. It really is fascinating. I think a lot of physicians today – and I think a lot of lay people today – still think of the cancer genomics as something in the future. There definitely is still a lot of research we still need to do, and we understand that, but aren’t there things going on right now, today, in cancer genomics, that are helping patients live longer?
Dr. Guest: Sure. And we are using the technology to reclassify diseases. We can do – for example, we can do testing for a gene called BRAF, B-R-A-F. If we find a mutation in that gene, that can actually change how we might approach the treatment for that patient. That’s a test that we regularly do in our lab. And there are a lot of other examples of tests like that. We have really felt like it’s not – we can’t just focus on the genes that are known because there are going to be so many more things out there to discover that are going to impact how we think about cancer and treat it.
What we’re doing at Children’s Mercy, is doing clinical testing, but at the same time, using research funding. We’re very blessed to have research funding from a lot of different community organizations from Black and Veatch, from Big Slick, from Children’s Mercy Cancer Center, and now, our new Children’s Research Institute. All of these funds, we’re putting them towards being able to do innovative research investigations for all of our patients with newly diagnosed cancer and with relapses so we can start to put all of the pieces of the puzzle together. All of that research in combination with research being done around the country and around the world is really going to help us advance the treatment for all children with cancer.
Dr. Smith: It does. To me, it seems that Children’s Mercy is really in a great position to be a leader and an innovator in cancer genomics. I think that’s very exciting for Children’s Mercy. Where do you see all of this going? It’s a fascinating field; it’s a big field. We’ve touched on just a little bit of it. What excites you most about this, and where do you see this going?
Dr. Guest: I think the things that really get me excited are particularly the single-cell sequencing and then looking at the RNA, those newer technologies that are going to go beyond just what the mutations are – and the methylation, as well. I think that – I imagine that in another five years, we’re going to be doing clinical testing that’s going to focus on looking at individual cancer cells. Right now, when we take a look at a tumor -- at least the standard way of doing that is to mash up all of those tumor cells, take all of the DNA out of all of the tumor cells all at once. If we can really understand what’s going on in each cell and how that changes over the course of months for a patients cancer, and if we can get down to the single-cell level where we can just do a blood test, and be able to – maybe a patient has a tumor in their leg bone, but if we can draw their blood and find the information that we need out of that test on an individual cell level, that’s going to cut back on a lot of invasive type procedures for patients and make sure a huge difference for their care.
Dr. Smith: Fascinating, yes. Wow, just such an exciting field. Dr. Guest, I think you’re just going to have to come on the show occasionally, right and give us an update of where everything is at and where we’re going because it really is such a huge field. I know that Children’s Mercy is a leader, there’s so much research going on, and I’m excited for you. I also just want to thank you for coming on the show, today.
You’re listening to Transformational Pediatrics with Children’s Mercy Kansas City. For more information, you can go to ChildrensMercy.org, that’s ChildrensMercy.org. I’m Dr. Mike Smith. Thanks for listening.