Genomic Medicine Translational Protocols – What Do They Mean for Patients Everywhere?

Genomic Medicine Translational Protocols – What Do They Mean for Patients Everywhere? 1024 614 Elizabeth Varga
abstract art of magnifying glass over DNA strand

As part of the Journey to Best Outcomes, Nationwide Children’s Hospital has dedicated significant resources to genomic medicine, named as a key accelerator in the 2017-2021 strategic plan and as one of the three pillars that will be utilized to integrate research and clinical care over the next five years. In response, the Steve and Cindy Rasmussen Institute for Genomic Medicine has expanded resources devoted to genomic medicine translational protocols.

Defined as projects that are meant to directly answer questions related to the diagnosis, prognosis and optimal treatment for patients evaluated across our hospital, translational protocols are vital to best outcomes. These protocols help to identify the genomic approaches that are best suited to understand the pathogenesis of individual disease, predict the best course of treatment, and eventually validate the highest yield assays for clinical use.


Proving the Concept: The Comprehensive Genomic Profiling for Hematologic and Oncologic Disorders Study

As proof of concept of this “n-of one” approach to improve patient care, the Comprehensive Genomic Profiling for Hematologic and Oncologic Disorders Study was launched in 2017. Since inception, this study has consented more than 400 unique patients with cancer, blood and vascular disorders to undergo comprehensive analysis, including sequencing of the protein-coding sequences of inherited DNA, as well as that in their tumor or affected tissue. The profiling has also included evaluation of the complete transcriptome allowing for better assessment of how genes are being expressed in the affected tissues.

In some cases, gene expression is turned off or on through a process referred to as methylation. This comprehensive profiling allows for comparison of methylation profiles between patients with different cancer types, as well as patients with similar tumors to obtain unique insights. In concert, the data gleaned has informed diagnosis, prognosis, and/or therapeutic choice in more than 90% of patients studied to date. Additionally, unique genomic alterations found through this approach have directly altered clinical decision making, as illustrated through patient stories.


Translating Research Findings to Clinically Available Testing

What makes the Genomic Medicine Translational Protocols unique is the intent to directly translate the findings from research to develop clinically available testing that can assist clinicians and patients at Nationwide Children’s and beyond. For example, the Institute for Genomic Medicine now offers three clinical tests that directly resulted from the experience with the cancer translational protocol, including a methylation array for central nervous system tumors, an RNA-fusion panel to identify rearrangements in chromosomes that could be targetable with a cancer therapy and a newly launched paired exome sequencing test to identify inherited and acquired genetic mutations that lead to cancer and other disorders.

These tests are offered at very few children’s hospitals and are uniquely available in house to patients evaluated at our facility. This translational protocol has also allowed for five years of partnership between clinicians and the laboratory. With this partnership, education, collaboration and a shared language have developed, resulting in a streamlined clinical transition and opportunities for Nationwide Children’s to pave the way in innovation and adoption of personalized medicine.


Expanding on Our Success: Neonatology

Replicating the successes in cancer and blood disorders, the Institute for Genomic Medicine seeks to expand into other service lines to offer increased access to cutting-edge genomic technologies.

With Nationwide Children’s commitment to fetal and neonatal services, a priority focus is providing rapid genomic diagnosis to critical newborns and children suspected of having a genetic disorder. With this in mind, a rapid genomic sequencing protocol was launched in 2020. This protocol has provided patients, families and care teams valuable information with results delivered in less than five days on average and a 35% diagnostic rate.

By identifying an underlying genetic cause of the child’s condition quickly, the child may be started on a precision therapy and/or allow the family to make informed decisions regarding goals of care while avoiding futile treatments. In addition, challenges to implementation have been identified, such as consent and sample collection for parents, which is important to recognize prior to launching a clinical test. This has allowed the research team to work with hospital leadership and administration to devise ways to overcome barriers, including bedside phlebotomy and virtual consent options. It has also increased collaboration between teams in the Intensive Care Units and The Division of Genetic and Genomic Medicine, leading to the creation of a full-time genetic counseling position within the Neonatal Intensive Care.


Continued Growth

Over the next five years, we look forward to continued growth and demonstration of the value of genomic medicine to benefit patients everywhere. We will continue ongoing efforts in the following areas:

  • Craniofacial malformations
  • Immunology and pathogen detection
  • Digestive and motility disorders

And we look forward to expansion into new service lines including:

  • Cardiology and critical care
  • Primary care
  • Fetal therapy

We will double down on efforts to create a biorepository of specimens available for use by research investigators. Through these collaborative partnerships, we believe the promise of genomics will manifest through direct translation, such that all clinicians and patients will experience its impact for generations to come.


Image credit: Adobe Stock

About the author

Elizabeth Varga, MS, CGC, is the director of Clinical Genomics Research and Development in the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital and is a licensed genetic counselor and adjunct assistant professor of Pediatrics at The Ohio State University. She oversees development and implementation of genomic research protocols into various services lines across Nationwide Children’s and manages the Clinical Genomics research team comprised of genetic counselors, research coordinators and data/regulatory staff.

Elizabeth has almost 20 years of clinical experience as a genetic counselor, with specific expertise related to the genomics of pediatric hematologic, oncologic and immunologic disorders. She has served on the Board of Directors for the National Society of Genetic Counselors and was a founding Board member of the National Blood Clot Alliance.