The amount of information gathered via next-generation sequencing has made the diagnosis of genetic disorders quicker and more accessible to clinicians than ever before, but with expanded testing options come questions about ordering the correct type of testing.
Each patient’s particular clinical situation is really the most important driver when deciding which type of genetic testing to order, according to experts who spoke during Monday’s morning symposium, “Is Bigger Always Better? Pros and Cons of Targeted vs. Comprehensive Genetic Testing.”
Linnea Baudhuin, PhD, and Carol Saunders, PhD, led an interactive session that sought to take some of the guesswork out of ordering complex genetic tests by outlining the pros and cons of ordering gene panels, whole-exome, and whole-genome testing. The speakers queried session attendees about the types of genetic testing offered at their institutions and quizzed them on which test should be ordered after learning details of several case studies.
“People should realize that there are benefits to both whole-genome and targeted analyses, and it comes down to ordering the appropriate test in the appropriate clinical setting,” Baudhuin said. There are many differences between the two types of tests that people are unaware of, she continued. In reality, whole-exome and whole-genome testing really are more like screening tests, due to limits of sensitivity—a fact not well understood outside clinical laboratories. However, in cases where a patient has a very non-specific phenotype, this type of testing makes more sense, she explained.
Another common misconception about this type of analysis is that it tests for “everything.” The truth is, current technologies miss a lot in the genome. “Hopefully most people realize by now that there are poorly covered or under-represented regions, “Saunders said. “As with any test, it’s important to realize the limitations.”
In spite of these constraints, the information clinicians gain can be very impactful. Saunders discussed several studies that emphasized the utility of rapid whole-genome sequencing. Almost half of the patients in each study had a change in clinical care based on the sequencing results and a similar number of patients received a final diagnosis that had not been considered by the clinical team initially.
Educating clinicians is a key element in effectively utilizing genetic testing. Both speakers also emphasized the importance of genetic counselors in this process. These key players serve as the face of the laboratory, gather additional clinical information about patients, and guide ordering of correct tests or offer alternatives when appropriate.
The need for clinician education does not stop once the correct test is ordered. Any type of genetic testing still needs to be interpreted correctly, a challenge that laboratories handle differently. The variant interpretation process is the main bottleneck of the testing process and also factors into the variable quality of results from different laboratories. Clinicians often don’t understand these factors, presenting still more opportunities for genetic testing results to be misinterpreted.
Analytics aside, whole-genome sequencing is more expensive to perform than targeted panels and whole-exome sequencing, with low reimbursement. In spite of this, in cases where the sequencing results are able to give a family an answer and halt a diagnostic odyssey, the cost savings could equal years of testing and treatments. “Whole-genome sequencing is an effective, albeit expensive, tool; until sequencing costs decrease, whole-exome sequencing is a good bet for most situations,” Saunders suggested.