Advanced DNA testing is allowing doctors to tailor treatments to individual patients, and to find out what diseases you might be at risk for, or already have. Dr. Debra Leonard explains in an interview. Listen at the link below.

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UVM Medical Center: Would you want to know? That’s a key question facing patients as the ability to examine and interpret a person’s DNA is growing. Being able to see all of your genetic information can uncover whether you already have a disease or disorder, if you’re prone to any, and what problems you might pass along to your children and grandchildren. It can also allow doctors to tailor treatments to you specifically, potentially increasing their effectiveness.


The UVM Medical Center is planning to make genetic information a centerpiece for prevention and treatment in the coming years, so we’ve launched an interesting research project to better understand what concerns, perceptions, and questions patients and providers have about all this. We’ll be hearing about that today and a lot more about this exciting area of medicine from a leading national expert who just happens to be the chair of pathology and laboratory medicine at the UVM Medical Center and the Larner College of Medicine at UVM.


Among other things, Dr. Debra Leonard has been an advisor to the US Department of Health and Human Services, a key participant in a landmark Supreme Court case about patenting genes, and is a founding member of the Association of Molecular Pathology. Before coming to UVM, she held leadership positions at Weill Cornell Medical College and New York Presbyterian Hospital. Thank you very much for coming.


Dr. Leonard: Thank you for having me here.


UVM Medical Center: Why don’t you start by helping people understand how does this work. How do I get my genetic information, and how do you guys screen it?


Dr. Leonard: First of all, let me explain what a genome is, because many people may not understand that. Inside each one of our cells is genetic material called DNA, shorthand for all the genetic material that’s inside of each of our cells. It’s the same in every single one of our cells, more or less. It’s just that each type of cell: a skin cell, a heart cell, a lung cell, a brain cell, uses different parts of that genetic information. The genome is all of that genetic information.


We now, because of work done with the Human Genome Project, which was an international project to obtain the sequence of a generic genome, and technologies that were developed after the Human Genome Project, we are able to sequence an individual patient’s pretty much entire genetic material. DNA is made up of four letters, if you consider your genetic material to have an alphabet. The letters are A, C, G, and T. So, what we get is a very, very long sequence of A’s, C’s, G’s, and T’s in a specific order that makes each person unique. Now, it doesn’t vary that much from person to person, because we’re all humans, and we all breathe and hopefully walk and see using the same genetic mechanisms; but the details, how the words are written to make us each individuals, is what makes you look different than me and me look different than other people.


UVM Medical Center: And you can determine if there is something wrong with one of those genes, something abnormal, right, that may indicate a problem.


Dr. Leonard: Exactly. A gene in the genetic material is a segment of the DNA that will encode one protein usually, and that protein is what does the work in your body. It can be a channel; it can be structural, like a muscle protein. When we look at the sequence of different genes in individuals, we can identify almost errors in the language of a gene, in the letters of a gene, to say that that gene will not make a protein that works the right way.


When we can tell that about someone, they may or may not have symptoms already, because sometimes a disease process happens after many years; so, that’s called the ‘age of onset’ of a disease. If it’s a childhood disease, then we usually start looking for the cause earlier. If it’s an adult onset disease, by the time we would do a genome sequence of a patient, they may not have started having those symptoms yet.


So, sometimes being precise about predicting when the disease might occur and how severe it would be is not always so accurate just from the genetic information, but it does allow us to be aware that a patient may be at risk for a disease, monitor them more carefully; so, if they do start having symptoms, we can pick up that disease earlier. Generally, the earlier you pick up a disease and start treating, the more effective that treatment may be.


UVM Medical Center: This is the preventive value, and this is a really significant preventive value that could have a big impact on medical care, right?


Dr. Leonard: Yes, and there aren’t too many studies saying how many people would benefit from genome sequencing. I know of a few cases of people who have had their genome sequenced and gotten unexpected results that they were not at all aware of, and some of those are quite life-changing. For example, one of the individuals had an unexpected breast cancer risk mutation, and that is usually treated proactively by bilateral mastectomy and removing of ovaries, which can be very challenging for a woman who has not yet had children. So, that’s a conversation and a decision with the patient. If they delay that very preventive strategy, they can be monitored much more closely for breast cancer in the meantime.


UVM Medical Center: The other value that’s talked about a lot is the precision piece, the so-called personalized medicine. Where are we at with that now? Is that something that’s commonly being used and is being helpful already, or is that more of a future thing?


Dr. Leonard: Oh, no. It’s happening today at the UVM Medical Center. Our plan with our program is not to immediately jump into genome sequencing, and so we’ve started with cancer testing. There are many genes that cause cancers, and depending upon the drivers, for a cell to grow too much and form a cancer is different from cancer to cancer. For many of those driver genes we have targeted therapies. On February 1st we went live with a 29-gene test for what we call ‘solid tumors.’ That’s breast cancer, colon cancer, lung cancer. That’s as opposed to blood cancers, which we’re going to do next.


With that 29-gene panel we are changing how some cancer patients are being treated here. Some cancer patients who are getting the targeted therapies are actually showing, in quotes … You can’t see my fingers … the “miracle cures” of a targeted therapy, and so that’s very exciting here at the UVM Medical Center.


UVM Medical Center: So, in other words, you can tell based on genetic information that this drug that we know about is effective with this particular thing. We know this person has a very specific kind of cancer, so this drug, we think, or combination of drugs, might be more effective with this particular person instead of just sort of trying what would be by-the-numbers “Let’s try this chemotherapy.”


Dr. Leonard: Right. Classically, chemotherapy has consisted of treatments that kill any dividing cell, and so that’s why your hair will fall out, and you’ll have mouth sores, and you could have other side effects, because normal cells are also having to grow and divide just to maintain you as a person. So, you’re killing those as well as the cancer cells that are growing too fast.


With the targeted therapies you are more targeting the specific mutation that is driving that cancer cell and not so much affecting the normal cells, so it’s much more effective in killing the cancer cells. Generally, you also use some level of generally cell-dividing, cell-killing treatment, but it doesn’t have to be as strong. So, the combination of the targeted therapy that’s specific to killing that cancer cell is quite effective.


UVM Medical Center: You’re listening to Dr. Debra Leonard. She is chair of pathology and laboratory medicine at the UVM Medical Center and Larner College of Medicine at UVM. We’re talking about genomic medicine, basically how your DNA information is being used now and even more so in the future to help develop the most effective treatments for you and to help with prevention of diseases you may have.


I think that’s sort of where I want to go when we move on here, which is, this is going to become more common. You have plans to have all of our patients at some point in the next several years have their entire genome screened. This raises this question about, what are people’s fears about that? What are the concerns? What do people know, not know about it? So, you’ve started a research project to find out what those concerns might be so you can figure out how to communicate. What did you do?


Dr. Leonard: Well, there’s a company called Illumina, and they have a program that they call Understand Your Genome, or UYG, and they partner with companies, programs, academic medical centers to provide genome sequencing to a group of individuals at a reduced cost. They provide a clinical report to the patient and their physician, and then each person who has had their genome sequenced gets their genome on an application so you can explore.


We partnered with Illumina to have a UYG program here at UVM, and 73 people had their genome sequenced. That is all finished. We partnered with a group at Harvard called People Seek that is looking at individuals who have had their genome sequenced to understand what motivated them to have their genome sequenced; what were their concerns; how much do they understand genetics and genomics; and then what do they do with their genome sequence after they get their results and get access to their genome.


We will look at the information that they’re providing to understand what processes we should do to engage with healthcare providers, patients, their families, and the public before we start doing genome sequencing. We don’t want the first patient to walk in and they are like a deer in the headlights, not understanding what’s being done.


UVM Medical Center: One thing I wanted to bring up before we close is, we’ve talked about the potential big upsides to this, but there are questions about potential downsides, the main one being these reports can reveal information that really isn’t conclusive, so may raise a concern, or worry: “There’s some indication that you might have a problem with this, but we don’t know. We don’t know the significance of it.” Or, say, at 50 years old, we can tell that you’re prone to have Alzheimer’s, but there’s no treatment for it right now; so, you’re giving somebody that burden of knowing that and not being able to do something about it. What’s your reaction to that concern?


Dr. Leonard: Actually, my grandfather, and I think my father, though he died a little early to be conclusively sure, had Alzheimer disease, and so the very first thing I looked at when I got my genome sequenced was whether I was at risk for Alzheimer, and I am not. I wanted to know, because I wanted to be able to plan for that. I might have increased my disability insurance. I might have taken steps. My husband says, “We’ve got this anyway. Why wouldn’t you want to know about it?” But my husband and I are also information seekers, and not everyone approaches concerning issues by seeking more information.


It would help your physician to potentially recognize earlier the symptoms of Alzheimer disease or some other disease. There are clinical trials for many diseases for which we don’t have good treatments … Treatments are being developed … and so enrolling in a clinical trial; also, being an advocate for developing treatments before you have the onset of symptoms. This points to the issue that the medical community has. The faster and the more accurate you can make a diagnosis, the more likely it is that you’re going to be able to help someone, but our diagnostic ability is limited by our own knowledge base, by our biases, and we’re also limited by the amount of time that we have with each patient.


The genome basically could help to broaden our diagnostic thought process and help us to reach a more accurate diagnosis. Part of the research that we’re also doing here around our first cancer test is, are we improving patient outcomes and are we improving the cost-effectiveness of the care that we’re delivering? Those questions don’t get asked that often by researchers, so this is some of the unique research that we’re doing here in Vermont around every genomic test that we’ll implement.


UVM Medical Center: Fascinating. Because there’s so much yet to be revealed, I’m sure we’ll have you back to talk about where you’re at, but for now we have to leave it there. Dr. Debra Leonard has been our guest on HealthSource. She is chair of pathology and laboratory medicine at the UVM Medical Center and Larner College of Medicine at UVM, a leading expert in genomic medicine. Thanks so much for coming.


Dr. Leonard: Thank you.


UVM Medical Center : You’ve been listening to HealthSource, brought to you by the University of Vermont Health Network, which includes the UVM Medical Center, Central Vermont Medical Center, Champlain Valley Physicians Hospital, Elizabethtown Community Hospital, and Alice Hyde Medical Center. For more information visit


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