A Way Forward in Genomic Medicine

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Charis Eng, MD, PhD, FACP

Our goal is to integrate genomic medicine processes into every clinical subspecialty at Cleveland Clinic.

—Charis Eng, MD, PhD, FACP

Over the past several decades, the convergence of scientific discovery, technology, and therapeutic developments has created an unparalleled opportunity to integrate our growing knowledge of genomics into the clinical practice of oncology. To shed light on the current state and future of genomics-driven cancer medicine, The ASCO Post recently spoke with Charis Eng, MD, PhD, FACP, ACS Clinical Research Professor, Chair and founding Director of the Genomic Medicine Institute at the Cleveland Clinic’s Lerner Research Institute.

Genomic Medicine Institute

Please tell the readers a bit about the Genomic Medicine Institute (GMI).

I founded the GMI about 8 years ago as a single platform for genetic and multi-omics research, academic clinical activities, and education in genomic medicine as it pertains to personalized health care. Before this, there was not even the practice of traditional medical genetics at the Cleveland Clinic. Actually, I am one of only four formally trained clinical cancer geneticists in the nation.

Since then, I’ve built out the clinical arm of the GMI, which we call the Center for Personalized Genetic Healthcare. It has become the nation’s most comprehensive center of genomic medicine, from the traditional prenatal and pediatric genetics to adult subspecialties like cancer genetics. Our research is very patient-oriented; the genetic and omics data we collect provides evidence-based cancer risk assessments to help guide clinical management of our patients.

In the past, it could take several months for a patient to get genetic services. By standardizing the practice and actually completely disrupting the practice of medical genetics, we have same-day access. Accelerating the process has obvious clinical benefits, but it also reduces patient anxiety.

Genetic Counseling

Our knowledge of genetics has rapidly expanded. Are we capable of fully using this knowledge in clinically meaningful ways?

Yes, [we can make good use of this information] if clinicians know where to send their patients for genetic counseling, which is a crucial component of utilizing genetic information for clinical decision-making. My team has worked to integrate genetic services and genetic counselors throughout the Cleveland Clinic system in the region and outside northeastern Ohio.

Our genetic counselors now serve in approximately 20 clinical locations associated with nine different specialties, both on and off our main campus. In fact, last year about 4,000 new outpatients saw genetic counselors, up from about 600 in past years. Our goal is to integrate genomic medicine processes into every clinical subspecialty at Cleveland Clinic.

Decision-Making Dilemmas

At the recent Society of Surgical Oncology meeting, you gave a lecture titled “Gene-Enabled Surgical Decision-Making: The Agony and the Ecstasy.” Could you describe some of the highlights?

The susceptibility gene PTEN that is being examined in Cowden syndrome makes a good genetics model, as many other heritable cancers flow along these lines. Generally PTEN mutations are found in 25% to 85% of people with Cowden syndrome, which confers a very high lifetime risk for several cancers—for instance, an 85% lifetime risk of developing breast cancer and a 25% lifetime risk of thyroid cancer. PTEN also confers a higher lifetime risk of developing colon, endometrial, and kidney cancers. So, we can predict a molecular diagnosis because we know the particular gene mutation. We even know the ages at which the risk rises within mutation-positive individuals.

When we predict an 85% risk for developing breast cancer, it’s a no-brainer that we need to screen and also consider prophylactic prevention measures. These women may also have benign disease, making screening difficult. However, with magnetic resonance imaging, we can pretty accurately predict cancer. Deciding on a clinical course presents certain dilemmas, but it’s still better to have to make hard decisions that might save a life than to not have that information. This knowledge, although imperfect, gives us an array of options.

The agony part of this issue—as it’s related to Cowden syndrome with PTEN mutation—is that in doing a total thyroidectomy, it is impossible to remove every single cancer cell; therefore, we actually see thyroid grow back. When thyroids grow back, the thyroid cancer risk comes back. So even though our genetic predictors give a reason for clinical intervention, the patient still must undergo periodic lifetime surveillance.

Moreover, because of the anatomic location of the thyroid, surgery is complicated and can result in scarring that makes follow-up surgery almost impossible. Again, it is great to have this genetic information, but we still need to know every clinical outcome associated with every variant (variant is used when one is not sure that it is a disease-associated mutation).

Genetic Screening Testimony

In 2009, you testified at a meeting of the Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) focused on evidence needed to evaluate screening genetic tests for Medicare coverage. Please explain how the federal government evaluated the potential of genetic screening.

It was essentially a fact-finding process in that they wanted guidance on what genetic screening entailed and where we could apply it in a way that would benefit the public health system. Prenatal genetic screening is practiced worldwide, but expanding that to adult populations in order to screen for factors that predispose people to cancer and other adult-onset diseases is an area that was still confusing.

The most interesting part is that all of us stood up and independently said that taking a family health history is the most effective and cost-efficient manner to screen for genetic disease. And although this meeting took place in 2009, CMS established two new “G” codes for family health history screening during the annual wellness visits.

In retrospect, it was a good experience; however, it also gave me a good look at the challenges we face in dealing with government agencies. The bureaucracy was stifling, even to the point of the instructions, which were terribly unclear.

Personalized Medicine

The term “personalized medicine” has captured the imagination of providers and payers. From your perspective, what does it mean and where are we going with it?

Yes, everybody loves the term, but most don’t know the meaning. The term personalized medicine was first coined by Pharma as a way to frame genomics in the drug development process, ie, pharmacogenomics. I use personalized health care in a larger health-care context.

Genetics is only one aspect of personalized health care. A human is not just one gene or even our 30,000 genes. You have to look at the whole landscape. Genomic personalized medicine should take into account the sum total of gene-gene interactions and gene-environment interactions. And it is one component of the continuum that moves from imaging all the way to prevention and treatment strategies.

Hopefully one day soon everyone will have comprehensive knowledge of genetic and genomics-based personalized health care, not only for treatment and disease management, but also in the equally important field of disease ­prevention.

Closing Thoughts

Any last thoughts on your work and what lies ahead?

The principle on which I founded the Genomic Medicine Institute is the study of common genomic processes that lead to different diseases.  Borrowing knowledge from other fields to inform cancer and vice versa actually makes research go faster. Finding the particular molecular switch that turns the process on in specific contexts is essential to determining who will develop the disease and, ultimately, how we can select targeted interventions to effectively treat or prevent the disease, as the situation demands.

We are currently achieving small parts of genetics-based personalized health care, especially in the practice of clinical cancer genetics. So that’s the focus of my work moving forward. ■

Disclosure: Dr. Eng is a member of the external strategic advisory board of N-of-One, and external scientific advisory boards of the Center for Personalized Medicine, Mission Hospital, NC, CareSource and Medical Mutual of Ohio; and external scientific advisory boards of EcoEos and GenomOncology (unpaid).