Next-Gen Sequencing: Expanded Genetic Testing in the Real World

Marshall L. Summar, MD; Brendan C. Lanpher, MD; Sean E. Hofherr, MD


September 15, 2014

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It Takes a Team

Dr. Lanpher: Access to genetics is variable across different regions. Patients should not be limited in terms of their options just because a geneticist isn't nearby. But make sure that you have someone who can help you understand these results -- a clinician, ideally -- and genetic counselors to help you and the family walk through these results.

Dr. Summar: It sounds like the counseling issues before the test is done are as important, if not more important, than those afterward.

Now, I will ask you both to speculate. Sean, what's next?

Dr. Hofherr: The problem is that for a long time, the technology -- whole-exome and next-generation sequencing -- has been isolated to large sequencing centers. Most of them were spun out of the whole-genome sequencing project. When physicians order a test, they fill out a sheet with the relevant clinical information on that particular patient to help guide the interpretation of results. You want the test to be performed and interpreted by those who have access to the physicians and the clinical information from the electronic medical record.

There has been a big disconnect between reference laboratories that are able to perform the test and the clinical centers that are ordering the test. That has presented a difficult situation, because variants are reported that are not clinically relevant to that patient. You could also be missing something that is important to that patient because it is, by necessity, filtered out.

Now that the technology is becoming much easier to use and the price is coming down significantly, a lot of the smaller, in-house molecular diagnostics laboratories that support genetics practices are going to be performing this test in a way that integrates the clinical group when they are looking through the results on any given patient.

Dr. Lanpher: That probably represents the best-case scenario.

Dr. Summar: Are you saying that we will see decentralization of the technology, going from when it was very expensive and performed in only a few sites to more of a cottage industry?

Dr. Lanpher: The integration between the molecular laboratory and the clinical team is what is necessary for the most useful, and most accurate, interpretation of the variants found.

Dr. Summar: You are describing a team made up of genetic counselors, geneticists, the molecular laboratory, and the diagnosticians -- people who can interpret and make sense of the sequence data.

Dr. Lanpher: It's an ongoing conversation. You are going back and forth between the molecular lab and the medical team to help build the story that integrates the molecular and clinical data. It's not as simple as just filling out a phenotype sheet.

Dr. Summar: This is very different from classic laboratory testing, and this is what people need to adapt to.

Dr. Hofherr: Correct. This totally changes the paradigm of how laboratory medicine is being performed right now and has been for the past couple of decades.

Dr. Summar: I would like to thank you both very much. We will revisit this topic in the future. Every six months, I suspect that we will find something new.


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