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As Genomics Increases the Complexity of Diagnostic Tests, the Role of Genetic Counselors Expands

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As researchers get better at linking mutations in genes to specific diseases, the number and complexity of genetic tests has exploded.

Over the last few years, single-gene tests for indications like cancer-causing mutations in the BRCA1 and 2 genes have been developed into multi-gene panels for a variety of inherited disorders, ranging from cancer syndromes to cardiomyopathy to intellectual disability.

More recently, academic medical centers have turned to exome sequencing to uncover the cause of Mendelian diseases in children that have eluded detection by other diagnostic tests, and some clinical laboratories are employing whole-genome sequencing now to find the typo in the genome that causes a patient's illness.

New sequencing technologies have also transformed the field of prenatal diagnostics, offering non-invasive testing options to screen for chromosomal disorders in early pregnancy.

The National Institute of Health's Genetic Testing Registry (GTR) currently lists more than 13,000 tests for about 3,700 conditions, compared to about 2,500 diseases for which genetic testing was available in early 2012. According to the GTR, 25 laboratories worldwide currently offer genetic tests based on either whole-exome sequencing or whole-genome sequencing.

But the results of the new genomic tests are not always clear-cut, and might generate unwelcome news: A variant of unknown significance might play a role in a patient's disease, but research has not yet proven that it really does. Or the search for the cause of a developmental disorder in a child might reveal that he is also at risk of developing cancer later in life.

Genetic counselors have always helped patients navigate genetic testing, explaining to patients ahead of time what the test might reveal, and after results are in what it all means for them and their families.

The advent of new genomic tests has both expanded and changed their roles, shaping their discussions with patients and creating new employment opportunities outside the clinical arena.

GenomeWeb spoke with four genetic counselors working in various organizations — two academic medical centers, a genetic testing company, and a genomic tools provider with a nascent diagnostic arm — about how genomics, and the capabilities of new sequencing technology in particular, has been changing their profession.

Expanding roles

As they have always done, genetic counselors continue to advise patients suffering from genetic diseases or at increased risk for disease — young women with breast cancer, for example, or families where multiple generations are afflicted by the same disease. But the nature of the new genomic tests has changed their conversations with them.

"The type of patient we're seeing has not changed, but what we are doing with them is different," said Rebecca Nagy, an associate professor of clinical internal medicine at Ohio State University, and the president of the National Society of Genetic Counselors. "It's changed from beginning to end."

For example, during pre-test counseling, rather than focusing on a single gene and specific results, discussions tend to be broader, covering the types of mutations the test might uncover, and what their implications might be. "And that's true whether it's a panel test, exome, or genome sequencing," Nagy said.

With exome or genome tests in particular, the chance of incidental findings and difficult-to-interpret results increases. "While the genetic counselor can't possibly cover every single finding that might occur within that test, they can certainly prepare the family for the types of results that might come out of it, and we can put them into categories," she said. "We talk with the family about what they want to learn, when they want to learn that, and how they want to learn it."

"The [counseling] process is the same, we're just dealing with different volumes of information," said Erica Ramos, a genetic counselor at Illumina, which offers clinical whole-genome sequencing tests through its clinical services laboratory.

Because the new genomic tests cover more ground, variants of uncertain significance are more likely to come up, Ramos said, and genetic counselors are more involved in deciding which results to report back to patients. Pre-test counseling is more important than before, too, because of the increased complexity of the tests. "It's just a natural expansion of what we've already done," she said.

Exploring a greater percentage of the genome in one test to explain rare diseases has also meant that more findings only have a few references in the literature, Ramos said, so she and her colleagues needed to become more familiar with databases that cover those rare cases. "It requires [diving] a little bit deeper into the literature and into the cases than maybe you encounter with cystic fibrosis carrier testing or even things like BRCA testing, because these are more established now," she said.

Training programs for genetic counselors have adapted to the new testing landscape by incorporating more genomics content, Nagy said, and the standards for accrediting the programs are constantly being revised and updated.

Students in the genetic counseling graduate program at the Icahn School of Medicine at Mount Sinai in New York, for example, are "very involved in clinical research in genetics," said Randi Zinberg, the program's director, including genomics studies that explore the diagnostic use of whole-genome and whole-exome sequencing.

"We have started teaching our genetic counseling students about genomics, and variant calling, and how to interpret and discuss this information with families," said Zinberg, an assistant professor of genetics and genomic sciences at Mount Sinai.

New opportunities

Along with the growth in the number of genetic tests has come an expansion of job opportunities for genetic counselors, some of them outside of clinical care. "There are counselors doing all sorts of different jobs that we never would have dreamed of 30 years ago," Nagy said.

While about two thirds of genetic counselors continue to work at university medical centers, hospitals, or medical facilities, according to a survey conducted by the NSGC last year, 9 percent reporting working at commercial diagnostic laboratories, a number that has increased significantly over the last eight years, Ramos said.

GeneDx, a commercial diagnostic laboratory that is owned by Bio-Reference Laboratories, for example, employs more than 20 genetic counselors, up from fewer than 10 four years ago.

Rather than explaining test results directly to patients, genetic counselors employed by a diagnostic laboratory often serve as a liaison to physicians ordering genetic tests, acting "as a kind of quality manager," Nagy said.

One of their roles is to make sure doctors order the right test for a specific patient, which some studies have found can help control healthcare costs.

"If a doctor sends in a test for full sequencing of a gene, but then writes on the test form that the patient's sister has already been tested and has this mutation, we know that this particular individual only needs testing for that mutation – they don't need what may be a test worth several thousand dollars, but a $100 test," Ramos said.

Amy Daly is a genetic counselor at Gaithersburg, Md.-based GeneDx, where she mainly deals with the company's whole-exome test, explaining to other healthcare providers, such as ordering physicians and genetic counselors, how it works, what it can identify, and what the best indications are.

Another big part of her job is to write up the results of the test into reports that are easy to understand by physicians. One of the big changes in recent years has been physicians from disciplines other than genetics ordering genetic tests, she said, such as cardiology, neurology, and immunology, and genetic counselors play a big role in explaining the tests results to them.

Clinical exome sequencing was not available when she graduated in 2007, and gene panel testing was just starting. Daly learned on the job how to interpret results from multi-panel tests, and how to direct follow-up for patients, "and now that's evolved into exome sequencing, which is panel testing in extreme because you are looking at thousands and thousands of genes," she said.

Many training programs for genetic counselors also expose their students to new types of workplaces, through internships at diagnostic laboratories or in government offices, for example, Nagy said.

Even within traditional settings, such as university medical centers, the role of genetic counselors has been evolving, partly through new opportunities enabled by genomics. For example, counselors are more involved in clinical research now, Nagy said, writing grant applications, identifying families that qualify for a study, writing institutional review board protocols, and collecting information about patients and their samples.

Shortage or not?

While demand for genetic counseling services is expected to grow in the future with the increase in available tests, many believe the number of genetic counselors today — about 3,000 in the US — covers the current demand.

"I don't think at this point there is a shortage of genetic counselors, necessarily," said Nagy. While this is hard to measure, there is little evidence right now of patients in need of genetic tests having to wait for counseling services, she said.

An exception is rural areas, where access to counseling services can be difficult. One possible solution is remote genetic counseling, either by telephone or Skype, Nagy said, and at least one company, InformedDNA, is specializing in this area.

"We haven't had too many issues getting genetic counselors when we needed them," said GeneDx's Daly, though it can be tricky to find experienced ones.

Rather than a lack of numbers, "I think a lot of the issue right now is more the ability of institutions to support genetic counselors," Ramos said. The informed consent process can be time-consuming, in particular for whole-exome and whole-genome tests, but billing and reimbursement for genetic counseling services is limited. Also, counselors cannot bill for their services independently at the moment, a limitation that the NSGC would like to change.

"I think as testing expands, there will be increased demand" for genetic counseling, said Nagy, and the NSGC is looking to expand available training programs, currently about 30 in the US that generate 200 to 300 graduates each year who she said have "no problem finding jobs at this point."

As genetic tests grow in complexity, the need to explain them will likely grow. Genetic counselors "are experts at communicating complicated information," Zinberg said, and as such will likely be interfacing with both healthcare providers and patients in the future.

"As non-geneticist physicians start ordering [exome tests], they are going to need someone to help them interpret all this information for patients, and I think that's where genetic counselors have a real opportunity to step in, because we have a lot of knowledge," Daly said.

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