Interview conducted by and article written by Tatsiana Verstak*
Part 1: An overview of genetic counseling at St. Jude Children’s Research Hospital
Genetic counselors are professionals who have specialized education in medical genetics and counseling to interpret genetic test results. They ultimately guide and support patients in making decisions regarding their genetic health. An interview with Emily Quinn, MS, CGC, provides insight into her profession as a certified genetic counselor at the Cancer Predisposition Clinic at St. Jude Children’s Research Hospital in addition to thoughts regarding the future of genetic counseling in clinical care.
What is a certified genetic counselor?
To become a certified genetic counselor, you first go through graduate school. It is a two-year Master’s program, where you are exposed to coursework that includes your basic science as well as counseling, psychology, and research ethics. So, it is a blend of those fields. After you graduate, you sit for boards, and then you become certified. That is the path to become a certified genetic counselor.
The field of genetic counseling has been around for a while; primarily it was more general pediatric genetics. For example, if a family has a baby with Down Syndrome, our training is in education so we would explain what a trisomy is to the family and explain how that can happen, the biological mechanism, in terms that are easily understood by patients who might not have much health literacy. With sequencing and genetic testing becoming much cheaper and more available, we have seen a huge peak in interest and desire of our services so our field is really booming. It’s been around for a long time, but cancer genetics has only been around maybe the last ten, fifteen years; primarily focusing on the BRCA genes and TP53, the mismatch repair genes. There is as many as 30 or 40 people in the country who offer pediatric genetic counseling services in the country so we are small but growing.
So my job at St. Jude: unfortunately, most of the time a kid gets sick with cancer it is just this really sporadic occurrence; it is due to chance. But my job is to help identify those families and those children where this is cause for concern that there may have been an inheritance or etiology of that cancer. And so I talk the families through that process: talk to them about whether or not genetic testing is of interest to them, coordinate the testing, and connect them with resources.
What is the process like?
I can give you a general overview of what a new clinic visit would look like for me; an easy example for me to give is a patient with retinal blastoma, a tumor-type. The retinal blastoma gene was the very first cancer gene that was cloned and it took some time before we offered clinical testing, but I think it was in the ‘80s that they first cloned that gene. We know that when kids have retinal blastoma in one eye that the majority of the time it is just this very unfortunate occurrence that happened in that one eye, but 10-15% of the time they were born with a genetic abnormality in the retinal blastoma gene that is called RB1. RB1 is in every cell in their body, so it follows Nuisance 2 Hypothesis, where they are born with one copy not working and the other copy just due to chance develops a mutation because it becomes inactive and that can be the underlying way a tumor is formed.
So we see all retinal blastoma patients referred to us in our Cancer Predisposition clinic. For the unilaterals, I sit down and will take their family history and see if there’s anything concerning. Typically, these family histories are not concerning; the child is the first one in the family to have retinal blastoma. Sometimes there can be other things that pop up in the family that can give us cause for concern for further testing. There have been times to offer other testing in addition to RB1 for the patients.
I work with a team: there are four of us that work as genetic counselors in our Cancer Predisposition Clinic and we have three clinicians, two physicians and one nurse-practitioner. Sometimes with the retinal blastoma patients I may see them by myself, sometimes in conjunction with another clinician who will perform a physical exam also looking for any concerning physical features that can be indicative of another genetic syndrome. Usually with mutations in RB1 you are not expecting to see any physical dysmorphology but there are other syndromes where you can and its possible for people to have two things. After the physical exam and the medical and family history are taken, I will provide an analysis: talk the family through what my thoughts are about the case, and then will talk to them more specifically about RB1, its functions, and whether or not this is information they would like to know. By in large, families do want to know; there are some families who say no but they are the exception. Almost everyone who comes to our clinic wants to do testing.
From that process we discuss what the potential results could be, and what the implications of those results could be. For example, if we find out that the child does have hereditary retinal blastoma, meaning they have a gene mutation in all cells of their body, we know they are at higher risk of developing other cancers over the course of their life because they have half of that tumor suppressor mechanism working in them. And then we can also utilize that information to test other family members: test to see if either the parents actually have this gene mutation but for whatever reason never developed retinal blastoma themselves, as well as test siblings. Then we can talk even further when the kid gets old enough. We like to see the retinal blastoma patients again when they are teenagers in clinic to talk about risks to their future children; we are always thinking long-term.
What do you think makes it different working with children versus adults?
I would say the biggest difference between working with an adult population versus a pediatric population is that for the most part, these children are not making these decisions for themselves. So it is their genes, their genome that we are doing testing on, and depending on the magnitude of the test, that can have very long-term consequences.
If the child is young or maybe has cognitive deficits or developmental delays, they may not be very engaged in that process as well. It’s very different when you are talking about testing someone who is not able to provide their own informed consent.
What happens when you do identify a child who has a genetic predisposition, do you enroll them in any research studies, or do you start gene therapy right away here?
With regards to the research studies, it depends. There are certain syndromes where there are national repositories and research studies that we will connect the families with. At St. Jude, our division has developed a number of surveillance protocols that we will offer to the families. There’s another genetic condition that I’ve seen fairly frequently in the clinic considering how rare it is, called Li-Fraumeni Syndrome and its caused by germ line mutations in the TP53 gene. Children, adults, everyone, with this mutation is at very high risk for developing cancer and because of that, we offer surveillance which includes total body MRIs, brain MRIs, as well as some blood work and ultrasounds.
We can’t prevent a cancer from happening, but the thought is if we can catch it early when the tumor is easiest to treat before it has a chance to spread to other organs that that will lead to an improved outcome. There are different groups of studies who have put out protocols very similar to ours that have demonstrated this to be very advantageous. But by in large, this is not nationally accepted yet. So in a way that is kind of offering clinical care, but under the research umbrella, in the sense that we do not know if insurance companies will cover this, but we feel that it is warranted. That all being said, when it comes to gene therapy, that is taking a gene mutation and going in and manipulating that mutation. So either cutting it out and replacing it with something or changing someone’s genetic makeup. That is very hard to do, there are many technologies and many research studies that are working to figure out the best way to do that. But that is not something that we are doing with any of our patients.
I know that at St. Jude, for example, there is a clinical trial for a bone marrow syndrome: they are going in and doing gene therapy on the bone marrow for patients with a particular bone marrow syndrome and that has promise. But if you are going in and trying to do this one genetic change in our huge genome of 20,000 genes, how do you know that you are only manipulating that one spot you are targeting? It is very hard to do, and it is very hard to feel confident that you are only manipulating that one spot.
In earlier gene therapy trials, they were finding that maybe they were finding a cure for whatever disease it was, but the long-term consequences were also not good and that for a while but a halt on gene therapy. I think that our advances and our modalities are better now and we are doing it at St. Jude, but we are not doing it in our division. It makes sense for bone marrow failure, because if it’s just the bone marrow that’s affected and you make a change to the bone marrow, hopefully that’s going to produce healthy blood cells and that’s all you are worried about.
Now with cancer predisposition, say we do gene therapy and we target bone marrow maybe that will help with predisposition to leukemia or other blood-born problems but that still isn’t going to make changes to the brain tissues or other tissues in the body that are not going to be affected by that. So we have a long way to go, but that is something that families do ask about commonly: so we have identified this gene mutation can’t we just fix it? The short answer right now is no, not right now. The longer answer is maybe, in the future, but I don’t dangle that carrot of hope for families that it is going to happen in their lifetime.
Are the children then involved in clinical trials after often they are identified with a gene mutation here?
It really depends on the syndrome. So for the retinal blastoma patients, no. I think that is something where it is a cancer type and a disease that we know well, and there are areas of research but generally no. Now there is another genetic syndrome called DICER1, where there are many registries; it is more newly described where we are connecting families with those resources. So it really is gene syndrome dependent.
Would you mind telling me a little about the St. Jude-Washington University Pediatric Cancer Genome Project (PCGP)?
I came at the end of when they were closing up that study, and it was a collaboration between Wash-U and St. Jude sequencing the tumors and the genomes of kids with cancer. I was involved in the germline: those healthy, normal cells and the genetic changes found there. Somatic or tumor genetic changes are interesting to me, it’s something I have learned about quite a bit since coming to this job but that’s not
my area of expertise, my expertise is in human genetics and the cells that you are born with, not tumor genetics. This study was comparing genetic changes in the tumor to healthy genetic changes. These were germline samples that were obtained from a bio repository that these families were consented to but these families were not aware that this genetic testing was being done on these children.
And everyone in the study was blinded to who these children were. Some of them were from St. Jude, some of them were from Wash-U, and as well as there were some larger repositories, too, that contributed to the PCG Project. From that, we learned that approximately 10% of these children had a genetic mutation that predisposed them to getting tumors, and that is a number that has been replicated at other institutions that have done similar studies. I think it was a little higher that anyone was expecting though. I think of it as Stage 1 of PCGP, and Stage 2 is clinical research, the Genomes for Kids (G4K) Project, which I have been very involved with from its start because it’s kind of the next step of PCGP where we demonstrated that we have the capacity and the pipelines to do these sequences and analyze these variants, but Phase 1 we were not disclosing results. These families were not being consented for this type of research and to learn this type of information.
Now for G4K, there is a study nurse who consents families although there may be a family who I see who I know may qualify for G4K and I will offer G4K as one methodology to do genetic testing as opposed to going to a clinical laboratory. With G4K we are sequencing, and this number may have moved from when it first started, but it was 565 genes in the tumor and 63 genes in the germline and comparing them. If in any of those 63 genes there is a mutation found, we were disclosing those results to families. We have been doing that for over a year and a half now. We have not yet published any of our findings from our study yet but by in large most of the families do want to participate. The reasons why families usually don’t want to participate are because they overwhelmed; usually it’s because the child has a very poor prognosis, and it’s just overwhelming to think about that at that time. There is a variety of reasons why families decline, but I think over 90% of families want to do it.
*Tatsiana “Tanya” Verstak, M.S. is a Contributor to Clinical Research Currents. She is a Pharm.D. Student at the University of Tennessee Health Science Center (UTHSC), a Research Associate at the UTHSC Office of Clinical Research, and a Pharmacy Intern at St. Jude Children’s Research Hospital. firstname.lastname@example.org
Citation for this article: Verstak, Tatsiana. “The present and future of genetic counseling: an interview with Emily Quinn, a certified genetic counselor at St. Jude Children’s Research Hospital.” Clinical Research Currents March 13, 2017. http://clinicalresearchcurrents.com