Helping All Medical Providers Understand Genomic Testing: Dr. Ethylin Wang Jabs, Mayo Clinic and Dr. Antonie Kline, Harvey Institute for Human Genetics

Caleb Furnas: Hi, I'm Caleb Furnas, welcoming you to Raise the Line with Osmosis from 

Elsevier, an ongoing exploration about how to improve health and healthcare. 

The increasing use of genomic testing over the last decade has created a need for greater education on its applications for diagnosis, screening, predicting disease risk, indicating how individuals may respond to drug therapies, and more. My guests today have stepped up to help the medical community understand the tenets and evolving concepts of genetics and genomics and how they might improve health care across disciplines by co-editing the book Genomics in the Clinic: A Practical Guide to Genetic Testing, Evaluation, and Counseling, published by Elsevier Science Direct. 

Dr. Ethylin Wang Jabs is the enterprise chair of the Department of Clinical Genomics for Mayo Clinic. She is also an adjunct professor in the Department of Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai and an adjunct professor of genetic medicine and professor of pediatrics at Johns Hopkins University.

Dr. Antonie Kline is the Director of Clinical Genetics at the Harvey Institute for Human Genetics at Greater Baltimore Medical Center in Baltimore, Maryland. She is also an instructor in pediatrics at Johns Hopkins School of Medicine and clinical assistant professor at the University of Maryland School of Medicine. Thank you so much for joining us today.

Dr. Antonie Kline: Thanks for having us.

Caleb: So I'd like to start with learning about what drew you to the field of genetics and how you applied it in your clinical work. Dr. Jabs, perhaps we can start with you.

Dr. Ethylin Jabs: Well, I just have loved the field of genetics for many, many decades. I think it was the caring of the patients, the very complex and rare conditions that we see in genetics that I found extremely interesting and so that drew me in, and I've been riding the wave ever since of genomics in terms of the type of technologies that have been brought forth in order to offer genetic testing to patients.

Caleb: And Dr. Kline, what about you?

Dr. Kline: Well, I enjoyed genetics in college and in medical school. Our instructor in genetics in medical school brought in patients and families to illustrate points in our first biochemistry class and after that, I went to the department and asked if I could work there, and I continued to work there through medical school.And then when I discovered that I liked pediatrics, I thought that was a great way to go into genetics. I too have been fascinated by the field. There's never a dull moment. We're always learning every day, and we're sharing information with families. So, it's really a wonderful field.

Caleb: To help set the table here, it would be great to get a big picture view of this field. How prevalent is genomic testing in medicine today and what are the most common uses of it? Dr. Jabs, can you give us your perspective on that?

Dr. Jabs: Well, really the practice of genetics is permeating and being implemented through the entire healthcare system, and I think you're well aware and everyone's well aware, it's in the news all the time. I think what brought it to the forefront is some of the technologies that we use in genetics when the COVID epidemic happened. I really think that we really need to educate all healthcare providers about the practice of genetics because they're going to be involved directly or indirectly in terms of genetic testing and conveying that information about what the results mean to patients and their families.

Caleb: Dr. Kline, would you add anything?

Dr. Kline: Yes, I do think that genetic testing itself is being used more and more by non-genetics providers. Often they will send gene panels or other tests directly on their own patients, and then when an answer is received that they might not understand, then they refer them for genetic counseling or a genetic evaluation. But I think that we feel that almost everything has something of a genetic basis, and it really, as Dr. Jab says, permeates everything in the field.

Caleb: For sure. So let's move to your book, Genomics in the Clinic. Dr. Jabs, you mentioned that one of the target audiences is clinicians. How do you expect this book to influence their work on a day-to-day level, and how do you envision that audience evolving over time?

Dr. Jabs: So, our target audience is really, as I said before, all healthcare providers. It includes non-geneticists, it includes primary care doctors, dentists, pharmacists, allied health staff, like nurse practitioners, and most importantly, it involves trainees. We want to really educate people, the younger generation, so it becomes second nature to them in their clinical practice.

I think what we have in our book is really essential concepts, and we're trying to integrate that into the current technologies that are available for genetic testing, the interpretation of genetic results, and how we can share this complex information with patients and families and make it understandable to them.

Caleb: Gotcha. Dr. Kline, I'm curious how you guys decided to tackle this big subject at this time and also, can you talk a little bit about the format?

Dr. Kline: Yeah, so it was a little bit of an evolving concept, but what we ended up with was that about a third of the book gives background in genetics and genomics, including definitions and explanations and different chapters for each aspect in genetics -- including genetic counseling, prenatal genetics, overall clinical genetics, genetic testing -- and then results and what to do with them, cancer genetics, and a few other topics. Two-thirds of the book are cases that parallel the chapters that I just mentioned and they describe typical case presentations, starting with the primary care provider or other type of specialist, what they should do initially in their workup and when to refer to genetics and the rest of the workup, the testing and results, counseling, family implications, and then the eventual outcome. 

Each chapter in the beginning of the book refers to multiple relevant cases, depending on the subject and then when you get to the cases, as concepts are discussed, it refers back to those explanatory chapters. The online version has links between these two sections, so we feel that that's kind of a unique aspect of our book. And then the last small chapter of our book describes how to communicate genetic results in a more lay person's terms with illustrations.

Caleb: Dr. Jabs, is there a case or two that are particular favorites of yours that you think illustrate the kind of education that you guys are trying to do that you'd like to describe?

Dr. Jabs: I would say every chapter is a favorite for me and they're all really interesting. I think Dr. Kline and I really have enjoyed doing this book and working with our colleagues. But I could mention an example. Let's talk about a cancer case. It was entitled Breast Cancer Gene Mutation Found Incidentally. The case is presented as a 32-year-old woman named Janet who schedules a same-day appointment with her primary care physician. At that appointment, she tells you, her primary care doc, that she recently was notified through a letter that she had the BRCA mutation, and she's now very worried about her risk for cancer. So she wants to talk to you, her primary physician, about what this means. 

And so we go through several of the issues that may be involved in an appointment like that. I mean, why is this important information? I think many of us as healthcare providers understand that if somebody has a BRCA mutation, it could potentially be disease causing. It increases the risk for having breast cancer, ovarian cancer, and even melanoma or prostate cancer. So it's really important that you care for this patient, and also you have to care for them in a very empathetic way because they're probably very anxious about getting this result. 

The next question that we as geneticists ask is we want to know how this result was given. Was there a document? It turns out in this case that she had actually enrolled in a research study. She did not do this as part of her clinical care, and she didn't have any symptoms that led her to saying she actually would have an increased risk for breast cancer at the time when she consented to this type of research testing. 

In fact, in this case, which makes it even more interesting, the research team recognized she had this change, but then she had moved out of state and they had to track her down. They tried to reach her by phone. Her contact information had changed. So they didn't get the result to her immediately.

The case goes on to talk about how valid this test result is, and we are very careful in making sure that the test result was done in a CLIA approved lab so that it was not a research result, because research results aren't always validated for clinical care. And then it goes on to discuss the types of management. What happens is they find out, yes, that the research team had used a CLIA certified laboratory to do the testing, and from there, they started telling her that she may be at an increased risk, and they referred to a high-risk cancer screening.

Then what is the management and some of the recommendations that are done? So I think this is a scenario that is not so unusual to our practice that we will hear this. And this will then be something that can happen in a family practice setting or your internal medicine doctor and so they need to be prepared how to handle these types of situations.

Caleb: Indeed. Dr. Kline, taking a step back, the last chapter is about ethical and social implications in genomic medicine. What's the purpose of including that and what sorts of concerns were you guys trying to address?

Dr. Kline: So, any kind of potentially predictive testing can have ethical issues related to it. It can also, if you are giving someone information pre-symptomatically, such as an increased risk for a potential future cancer, for example, then that could relate to insurance coverage, although by national law that shouldn't be an issue. That can lead to much anxiety in the family. It can also make the individual interested in having other family members tested, or at least to find out about it and it branches out from there.

There's also protected laws for minors. Sometimes parents will want to have their child tested for something that really has no relevance until they're an adult, and so some of these issues are covered in this chapter.

Caleb: You also included a chapter on direct-to-consumer testing, which has become quite popular. I know I get advertisements in my various social feeds for these kinds of things. What do want your readers to know about that?

Dr. Kline: Well, I think lay people are urged to undergo genetic testing, like you just mentioned. And if they decide to go ahead, sometimes, potentially, the results can be very misleading. For example, some of the more popular kits will say negative for breast cancer and it turns out they've only looked at three mutations in two different genes and they're saying no risk for breast cancer, whereas we know there's at least forty-five genes that should be looked at and also taken into context with the family history. So, we get concerned about false reassurance.  Then probably on the other side, somebody might come up with an answer that could cause undue anxiety for something that wouldn't matter as much.

Caleb: So in closing, we like to ask big picture questions to all of our guests. So, Dr. Jabs, I'll start with you. We have many students and early career health professionals in our audience. What's your advice to them about meeting the challenges of this moment and approaching their careers in healthcare?

Dr. Jabs: I would say that all trainees really need to have a solid foundation of knowledge for genetics and genetics testing because even if it's not implemented in the practice that they're currently involved in, it will be in the future.

Caleb: Got it. Dr. Kline?

Dr. Kline: Yeah, I think everyone needs to be aware that a genetic aspect of whatever they're looking at can be very important. I think they should consider family history as part of the background and if they're addressing something that doesn't quite feel straightforward, they should consider taking a step back and thinking, could this be something genetic, nd is there a bigger picture than what they're looking at? I think that would be an important lesson.

Caleb: Gotcha. Amazing. Well, thank you very much, Dr. Jabs and Dr. Kline for being with us today. 

Dr. Kline: Thanks for having us. 

Caleb: I'm Caleb Furnas. Thanks for checking out today's show. Remember to do your part to raise the line and strengthen the healthcare system. We're all in this together.