Pushing the envelope on personalized medicine

Eye on Innovation

In an era of individualization, when everything from entertainment to eyewear can be customized, healthcare has emerged as an area where personalization has a profound punch. From targeted cancer treatments and gene-based therapies to predictive disease testing and therapeutic drug monitoring, personalized medicine confronts illness at an individual level, using genetic clues to guide care.

The cornerstone of personalized medicine is genetic testing, which avails precise information on genetic variation that interferes with normal biological processes. Identification of these variants, sometimes referred to as mutations, enables tailored interventions that minimize the effect of the particular disruption.

“At this point, genetic testing can impact pretty much everybody,” says Ann Moyer, M.D., Ph.D., a genetic molecular pathologist and vice chair of the hereditary practice. “It could be people who actually have a disease and used for diagnosis or prognosis. You could use it for pharmacogenomics (PGx), or testing people if they're going to be taking a medication. People could be having babies, and in that case, they could receive carrier screening and/or noninvasive cell-free DNA prenatal screening to predict or plan for potential disorders in their children.”

With between 21,000 and 25,000 genes in the human genome and genetic variation being implicated in more and more diseases, finding the right diagnostic tools to pinpoint aberrant genes can be complicated. Accessing tests for variants associated with rare disorders, 80% of which are genetic in origin, can be even more challenging.

While foundational genetic testing has been available through Mayo Clinic Laboratories for decades, over the past few years the genetic testing portfolio has begun expanding. In 2022 whole genome sequencing was launched and whole exome sequencing was relaunched. Broader use of next-generation sequencing (NGS) technologies in MayoComplete oncology and hematology testing was also implemented in 2022.

In 2023 the genetics test menu ballooned. The Division of Laboratory Genetics and Genomics launched upwards of 30 new molecular and biochemical tests, and 35 others were upgraded. In 2024, more than 15 new assays are planned for implementation, with dozens more in active development.

“We've really had a commitment to say if you demonstrate clinical relevance, we will try and build a related test,” says Sounak Gupta, M.B.B.S., Ph.D., a genetic molecular pathologist and vice chair of the oncology practice. “Currently we have a lot of tests in the single gene space, a lot of medium-sized panels, and a lot of the large panels. We have found the best strategy is just to have multiple offerings, to let providers select the test that best meets the needs of their patient.”

The availability of custom gene ordering (Mayo ID: CGPH) allows for even deeper testing customization through tailored curation of gene panels.

A penchant for personalization

When it comes to the information we seek, we crave customization, says genetic counselor Carrie Lahner, who began working in the genetic disease space at Mayo in 2006.

Carrie Lahner, M.S., CGC

“We want everything personalized, so it makes sense that we want our medicine personalized at this time too.”

Carrie Lahner, M.S., CGC

Genetic medicine has also been driven by the conclusion of the human genome project in 2003 and a growing body of knowledge on how genetic information can be parlayed to predict and prevent illness.

“Even in my first position, I remember key opinion leaders across the institution saying, ‘Genomics is coming at us like a freight train; we have to make sure our staff is able to translate the science to the bedside,’” Lahner says.

In Mayo Clinic’s Department of Laboratory Medicine and Pathology, the intersection of scientific discoveries and hands-on, clinical expertise supports the development of clinically meaningful tests.

“One of the benefits of Mayo is that we have such a broad team,” says genetic counselor April Studinski Jones. “The depth of knowledge within those individual sub-teams is so deep that as new conditions and new diseases are being described in the literature, we are able to look at our existing tests and ask, ‘Do we have something that would apply to this disease state? Do we have something that would help confirm the diagnosis for these patients?’”

Ann Moyer, M.D., Ph.D.

"This integrated approach to test development — where patients’ needs remain at the center of the equation — is unique among medical institutions," Dr. Moyer says.

“One thing that can't be overstated is we are not developing tests in isolation,” Dr. Gupta adds. “Every time we build a disease-specific panel, we're just one phone call away from disease experts within the institution. If I want to build an endometrial cancer-specific panel, I can call up a medical oncologist and say, ‘How would you use this test?’ and ‘If I build it this way, what would the shortcomings be, what genes are we missing?’”

Creating a detailed genetic picture

The expanded genetics test menu available through Mayo Clinic Laboratories touches many aspects of genetic illness.

Testing to confirm a diagnosis of metabolic disorders, or inborn errors of metabolism, is among the new biochemical genetic assays. Detected through newborn screening and diagnostic testing, these rare disorders can result in severe physical and neurological impairment when left untreated. Several updates align with changes to the Recommended Uniform Screening Panel (RUSP), among them the addition of Hunter syndrome (MPS II) to newborn screening tests for lysosomal and peroxisomal disorders (Mayo ID: LDALD and Mayo ID: PLSD).

Dozens of new NGS oncology and hematology tests, from comprehensive multigene panels to single gene tests, were launched. Liquid biopsy testing was also implemented.

“On the oncology side, they've been able to test the tumor for a specific mutation and then use that to figure out what therapy is going to be the best to treat that person's cancer,” Dr. Moyer says. “Now we're using genetic testing not just for diagnosis, but also to guide therapy more on the hereditary side, too. Knowing the gene or specific variant that is causing a patient’s disease can lead to selection of a more specific therapy, or can lead to avoiding a particular medication. A drug was recently approved for Alzheimer’s disease, lecanemab, but before using it the FDA recommends a genetic test to assess the status of the APOE gene to determine if a patient should avoid the drug due to adverse risk.”

New, innovative testing technologies, such as droplet digital PCR, were also implemented, allowing for the development of a new test for mitochondrial heteroplasmy (Mayo ID: DMITO) and an upgraded test to analyze the TERT gene promoter (Mayo ID: TERTD), which is implicated in a number of cancer types.

Testing for inherited immunodeficiencies and immune dysregulation, such as viral susceptibilities (Mayo ID: VIRID) and familial hemophagocytic lymphohistiocytosis (Mayo ID: HLHGP), is another area that has expanded.

Simply having a vast menu of genetic tests, however, won’t necessarily provide personalized answers, Dr. Gupta says.

“Part of practicing personalized medicine is to be good stewards of the resources that we have available to us,” Dr. Gupta says. “With personalized medicine, I think we can decide which patients need more detailed molecular testing and which patients may not need that level of testing.”

Whether straightforward or complex, every Mayo Clinic patient and each test order is given the same level of care and discernment, Lahner says.

“It’s a multidisciplinary effort to diagnose these complex patients,” Lahner says. “We're not filtering everybody into an exploratory testing funnel because there may be supplemental assays that are needed or gene-specific consultant knowledge for patients who present with certain clinical features. We recognize the value in doing panel-based testing before you reflex to exploratory testing for some patients.”

Innovating at the edge of discovery

April Studinski Jones, M.S., CGC

The pace of discovery within the genetic space is fueling the test development pipeline, with nearly 50 new biochemical and molecular genetic tests currently in development and more than 15 slated for implementation in 2024.

“Every couple of months, if not every month, there's some new therapy that's being FDA-approved or getting other attention,” Studinski Jones says. “Treatment is really changing for genetic conditions and the ripple effects of that really come through in the genetic testing space.”

One of the benefits of working within Mayo’s integrated network is the ability to translate medical need into action, Dr. Gupta adds. Recently, for instance, a colleague alerted him that a gene for endometrial cancer had been identified as clinically important by several international medical associations, but Mayo Clinic Laboratories did not have a test for it. A discussion ensued about how best to test for the gene, and a new assay was built.

Sounak Gupta, M.B.B.S., Ph.D.

“We have the ability to be flexible, to synthesize everybody's collective knowledge, and say how can we push the boundaries in terms of our everyday daily work and at the same time democratize those same tests to everybody that has access to our services,” Dr. Gupta says.

“Our job isn't over right now that we've launched 50 tests. We're looking at what should be the next 50. It’s a continuous process — we never say we’re done.”

Sounak Gupta, M.B.B.S., Ph.D.

At Mayo Clinic, that unique collaboration is the engine driving advanced genetic testing.

“It's just an exciting time to really be in genetics as a whole, and especially in laboratory medicine where we can correlate and collaborate with our colleagues, who are also doing functional studies and serologic testing and all of the other types of tests where they have deep expertise,” Dr. Moyer says. “We're just really lucky to be in a place that is so collaborative because that's really what drives forward the most innovation.”

For patients relying on personalized answers to move forward in life, innovation holds the promise of clarifying the road ahead.

“This testing aligns with Mayo Clinic’s core vision, to diagnose the undiagnosable,” Lahner says. “That is what Mayo Clinic is consistently known for and Mayo Clinic Laboratories has developed a comprehensive suite of genetic testing that can do just that.” 

Learn more about genetic testing available at Mayo Clinic Laboratories.

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Robin Huiras-Carlson

Robin Huiras-Carlson is a senior marketing specialist at Mayo Clinic Laboratories and a Mayo Clinic employee since 2015. Her writing focuses on specialty testing, innovation, and patient-focused initiatives.