Next generation sequencing: What it means for patient care
Decades of research are finally paying off. Next generation DNA sequencing is now providing healthcare professionals with unprecedented insight into their patients' physiology.
Next generation sequencing (NGS) is a technology that reads the molecular instructions within cells. It already routinely supplies diagnoses for many genetic conditions. It also guides many aspects of cancer care, including therapy selection. These uses, however, may just be the tip of the iceberg as the technology continues to evolve.1
Not only have analytical capabilities grown, but the interpretation of sequencing data has also improved, making this technology more accessible to providers. This includes community physicians with no specialized training in genetics.
The increasing adoption of this technology is part of a shift toward personalized medicine. This new approach can tailor interventions to fit each patient's unique genetic background.2
"Suppliers offer a range of products tailored to different budgets, throughput and application needs, and we're starting to build our suite of product offerings in this space," says Diane Bernstine, director of business development, lab innovations at McKesson Medical-Surgical.
Here's what you need to know about NGS and how it's changing patient care.
What is next generation DNA sequencing?
In 2003, after 13 years of work, researchers defined the sequence of the human genome. Since then, sequencing technology has improved dramatically. It's now possible to determine a genome in mere hours.3 Meanwhile, the associated costs have also fallen dramatically since those early days. "This is critical as labs and clinicians today are under increasing pressure to do more with less," adds Diane.
The current version of this technology is known as NGS. Sometimes called high-throughput sequencing, it simultaneously reads the sequences encoded within millions of pieces of DNA. This represents an enormous increase in volume over previous methods which were more laborious and costly, and performed tests focused only on specific regions of DNA.4
NGS, by comparison, enables providers to sequence whole genomes and sections of them called exomes, as well as to profile gene expression. With this data, providers can identify the most effective treatments for their patients quickly and without trial and error.
How are clinicians currently using NGS?
Like the more constrained genetic tests that preceded it, NGS is often used to screen for disease mutations or to provide a diagnosis. However, this technology goes further, making it possible for providers to predict risk, select therapy or determine a prognosis based on a patient's own genetic background.2
Here are some of the areas where clinical practices in the U.S. have adopted this technology:
- Safer prenatal testing: NGS tests can detect chromosomal abnormalities known to cause developmental disorders, including Down syndrome, with high sensitivity and specificity. By analyzing DNA from the mother's blood, these tests offer an accurate and noninvasive method of screening for these disorders5
- Comprehensive cancer care: NGS is becoming increasingly important in cancer care. Screening tests can spot genetic variants associated with an increased likelihood of malignancy. Meanwhile, tumor DNA has proven to be a powerful source of information. By examining mutations within it, NGS testing can, for example, help providers predict the cancer's behavior. This includes the risk of metastasis, chance of survival and response to chemotherapy.2 Because NGS can identify dozens or even hundreds of potential mutations in a single test, it can glean large amounts of information from a small tissue sample6
- Anticipating drug responses: Genetic variations can determine how patients respond to certain medications. The labeling on some drugs, such as the blood thinner warfarin and the antiretroviral Abacavir, recommends genetic testing before they're prescribed.2 By analyzing markers related to drug metabolism, NGS pharmacogenomic tests can help to make sure patients receive effective treatment and eliminate potentially dangerous adverse events
- Diagnosis of genetic disorders: Sequencing the genomes or exomes of patients and family members has become a standard approach to identifying the cause of rare genetic disorders. In a recent study, researchers in the United Kingdom used genomic sequencing as part of their search for the causes of unknown disorders in nearly 4,700 patients. Their efforts led to a genetic diagnosis in a quarter of cases.7 Another study, this one of acutely ill infants suspected to have genetic diseases, found that whole-genome sequencing resulted in better, more focused care8
- Predicting risk: Nearly all diseases have some genetic component. However, that genetic contribution is often complex. Increasingly, more providers are using genetic testing to predict individual patients' risk for disease.2 Many such NGS tests are already available. They involve sequencing panels of genes linked to Alzheimer's disease and dementia, macular degeneration, colorectal and endometrial cancer, for example. With this information, providers can ensure that those most at risk receive preventative care, such as more frequent screening
- Assessing transplants: To monitor the risk of rejection after an organ transplant, providers may conduct biopsies. However, new NGS tests are beginning to offer an alternative. By profiling gene expression in blood cells, they can now identify patients whose bodies are rejecting heart transplants2
What's next for next generation DNA sequencing?
The genome-oriented care driven by NGS is only expected to grow. By one estimate, more than 60 million patients are going to have their genomes sequenced by 2025.9 Meanwhile, new applications for sequencing are emerging. And the technology itself is advancing.
Here's what's on the horizon and, in some cases, already starting to arrive in clinics:
- Liquid biopsies: Traditional biopsies are invasive. But some providers now have an alternative: identifying tumor DNA from within a blood sample. In 2020, the Food and Drug Administration approved the first such liquid biopsy, which detects mutations in a specific gene found in a form of lung cancer10
- Polygenic risk scores: Numerous changes within the genome likely influence the risk of complex diseases, such as coronary artery disease. By assessing these variations, it's possible to calculate a score indicating how likely a patient is to develop a condition compared to someone else. Such a score could guide decisions about healthcare or even lifestyle11
- Pre-emptive pharmacogenomics: Before prescribing a high-risk medication, providers can now assess how that patient's genetics may influence his or her response to it. However, in the future, testing for key variations could instead take place as part of standard care, then remain on hand in case the information is needed12
- Long-read sequencing: In spite of its power, next generation sequencing has limitations. This technology can read only short segments of DNA, limiting its ability to detect some genetic variations. Another technology, called long-read sequencing and sometimes third-generation sequencing, addresses this shortcoming. However, long-read sequencing is not yet ready for routine clinical use13
A new era for medicine?
As medicine has been traditionally practiced, a patient's condition, not that person's individual characteristics, has primarily determined the care he or she receives.
NGS technology is a driving force behind the current shift toward more precise, tailored care. In the process, NGS tests are reducing the need for invasive procedures. They're also supplying information that empowers providers — and patients — to make the best possible treatment decisions, the first time around.
"While no one can predict exactly when this new generation of testing will become mainstream, personalized, predictive care that fits each patient's unique genetic profile is an exciting future to envision," shares Bernstine.
A 2021 article on the future of next-generation DNA sequencing highlighted the views of industry and innovation leaders in this space, including Andy Felton, vice president of product management at Ion Torrent. He says "it's highly likely that you're going to have a blood-based cancer test in the next five to 10 years that is going to detect the early presence of cancer, and that's going to be routinely used to monitor your health."14
Be advised that information contained herein is intended to serve as a useful reference for informational purposes only and is not complete clinical information. This information is intended for use only by competent healthcare professionals exercising judgment in providing care. McKesson cannot be held responsible for the continued currency of or for any errors or omissions in the information.
© 2022 McKesson Medical-Surgical Inc.