How to Integrate Genomics into Clinical Practice

Clinical genome and exome sequencing (CGES) as a diagnostic tool is altering practice for clinical geneticists, genetic counselors and other clinical specialists.

The Clinical Genetics Think Tank (CGTT) has identified five areas of focus for the integration of CGES in clinical practice: the pretest process, pretest education for patients and providers, phenotyping, sequence data interpretation and posttest patient care. These areas are the topic of a paper published online in May in Genetics in Medicine.

“These key issues are all critical to the successful implementation of clinical genomics,” says Gail Herman, MD, PhD, clinical geneticist at Nationwide Children’s Hospital and a CGTT member. “Some institutions may be further along than others in each aspect, but these are challenges that we all need to address.”

The pretest process addresses the challenge of determining which patients should have CGES, who should order the tests and how the costs should be covered. The CGTT algorithm presented in the recommendations offers a streamlined and consistent process for determining who is most likely to benefit from CGES.

Once a patient is determined to be a good candidate, educating the patient and family about the benefits and limitations of CGES are expected challenges. But pretest education and training is also important for providers and insurance and government stakeholders. Key areas of education for these groups are the validity and utility of CGES in the diagnosis and treatment of patients.

The need for a common language for phenotyping is a familiar challenge to genomics researchers around the world. With utilization of CGES, the importance of phenotyping ontology – consistent terminology for describing symptoms, physical features and diagnoses – enters the spotlight.

“A common ontology to describe phenotypes is essential to good data management, cohort building and ultimately patient care. It should be incorporated into the clinic and the electronic health record as soon as possible,” says Dr. Herman. “This is an issue that needs to be addressed at all institutional levels and is critical to conducting genomics.”

Once a patient has CGES, even the best analysis doesn’t yield a definitive answer in every case. Yields are increasing, and methods are improving. However, the possibility remains that the variant causing a particular patient’s symptoms simply hasn’t been discovered or identified as pathogenic at the time of testing. So how often should the sequence data be reinterpreted?

“No one knows the answer to this right now,” says Dr. Herman, who is also a principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children’s. “We don’t have a lot of data to even look for patterns at this point. Moving forward, networks of sites working together will track the frequency of new variant discoveries and attempt to answer this question.”

Once the tests have been completed and the results are in, the posttest patient care phase lasts a lifetime. In some cases, genetic diagnoses will be used to influence the care of a generation and beyond. This cycle of evaluation, education, testing, analysis and reanalysis, follow up and education lays the groundwork for a new era in medicine for generations to come.

Reference:

Bowdin S, Gilbert A, Bedoukian E, Carew C, Adam MP, Belmont J, Bernhardt B, Biesecker L, Bjornsson HT, Blitzer M, D’Alessandro LCA, Deardorff MA, Demmer L, Elliot A, Feldman GL, Glass IA, Herman G, Hindorff L, Hisama F, Hudgins L, Innes AM, Jackson L, Jarvik G, Kim R, Korf B, et al. Recommendations for the integration of genomics into clinical practice. Genetics in Medicine. 2016 May 12. [Epub ahead of print]