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New Case of Polio Diagnosed in New York, Poliovirus Found in Wastewater in Two Counties

Experts say it is time ‘to restore our confidence in vaccines’ as many medical laboratories take steps to support testing for the polio virus

Clinical laboratories and microbiologists in the state of New York will want to know that, in July, a man in New York was diagnosed with polio and subsequently the virus was detected in the wastewater of two New York counties.

The area, Rockland County, N.Y., just north of New York City, was also at the forefront of a measles outbreak that occurred in 2018 and 2019. The outbreak was attributed to low vaccination rates within the community.

The unidentified, immunocompetent young man was admitted to a New York hospital after experiencing a low-grade fever, neck stiffness, back and abdominal pain, constipation, and lower extremity weakness. He eventually developed paralysis from the disease, which is irreversible. 

Poliomyelitis, commonly known as polio, is a disabling and life-threatening disease that is caused by the poliovirus. Though it rarely surfaces in the United States, there is now confirmation of the first US case since 2013.

Mary T. Bassett, MD

“The polio vaccine is safe and effective, protecting against this potentially debilitating disease, and it has been part of the backbone of required, routine childhood immunizations recommended by health officials and public health agencies nationwide,” said Mary T. Bassett, MD (left), Health Commissioner at the New York Department of Health, in a press release. Clinical laboratories and microbiologists in New York may want to prepare for an increase in vaccination requests. (Photo copyright: Time.)

Is Polio Back in America? Clinical Laboratories Will Want to Be Prepared

“I think it’s concerning because it can spread,” epidemiologist Walter Orenstein, MD, Professor, Department of Medicine, Division of Infectious Diseases at Emory University School of Medicine told STAT. “If there are unvaccinated communities, it can cause a polio outbreak.”

According to the federal Centers for Disease Control and Prevention (CDC), public health experts are working diligently to discover how and where the infected individual contracted polio. The CDC website states that the risk for people who have received the polio vaccine is very low, but there is concern for those who have not received the recommended doses of the vaccine.

“Most of the US population has protection against polio because they were vaccinated during childhood, but in some communities with low vaccine coverage, there are unvaccinated people at risk,” the CDC noted. “Polio and its neurologic effects cannot be cured but can be prevented through vaccination.”

The US uses an injectable polio vaccine for the poliovirus which contains killed viruses. The vaccine “instructs” the immune system to recognize and combat the virus. This inactivated polio vaccine (IPV) is administered to children as a shot in the arm or leg and is typically given in four separate doses.

“The inactivated polio vaccine we have is very effective and very safe and could have prevented this,” Orenstein told STAT. “We need to restore our confidence in vaccines.”

“Based on what we know about this case, and polio in general, the (New York) Department of Health strongly recommends that unvaccinated individuals get vaccinated or boosted with the FDA-approved IPV polio vaccine as soon as possible,” said Mary T. Bassett, MD, Health Commissioner at the New York Department of Health in a press release.

Poliovirus Found in Wastewater via Use of Gene Sequencing

Poliovirus is very contagious and is transmitted through person-to-person contact. The virus lives in an infected person’s throat and intestines and can contaminate food and water in unsanitary conditions. According to the CDC, typical symptoms of the illness include flu-like symptoms such as:

  • Sore throat
  • Fever
  • Tiredness
  • Nausea
  • Headache
  • Stomach pain

Most of these symptoms will disappear within five days, but polio can invade the nervous system and cause more serious complications, such as meningitis, paralysis, and even death.

After confirmation of the new case of polio, wastewater surveillance detected the presence of the poliovirus in Rockland and Orange counties, New York.

Wastewater analysis can uncover pathogens within a community and has been used in the fight against other infectious diseases, including:

“In some regards, wastewater is a public health dream scenario,” said Mark Siedner, MD, an infectious disease doctor at Massachusetts General Hospital and associate professor at Harvard Medical School, in an interview with Fortune. “Everyone poops, and most people poop every day. It provides real-time data on infection rates. In that regard, it’s an extremely powerful tool, particularly good at detecting early warning signs. Before people get sick, we might get a signal.”

Wastewater analysis can provide insights regarding the types of viruses that people within a community are shedding and if the volume of those viruses are increasing. This information can provide scientists with an early marker for an outbreak of an illness that is on the verge of spreading.

Microbiologists and clinical laboratories should be aware of the specific types of infectious agents public health authorities are detecting in wastewater, even as they perform screening and diagnostic tests on their patients for similar infectious diseases.

Polio is Appearing Worldwide

The Global Polio Eradication Initiative (GPEI) has announced that new cases of polio have been reported in Israel and the United Kingdom. These are countries where polio cases are extremely rare. 

This indicates that microbiologists and clinical laboratories managers will want to be on constant alert for uncommon infectious diseases that may appear suddenly, even if those illnesses are rare. Accurate and immediate diagnoses of such infectious diseases could play a major role in triggering a public health response to control potential outbreaks while they are in their earlier stages.

JP Schlingman

Related Information:

N.Y. State Detects Polio Case, First in the U.S. Since 2013

US Polio Case Tied to Viruses Detected in UK, Israel, Suggesting Silent Spread

New York Adult Diagnosed with Polio, First US Case in Nearly a Decade

New York State Department of Health and Rockland County Department of Health Alert the Public to a Case of Polio in the County

Public Health Response to a Case of Paralytic Poliomyelitis in an Unvaccinated Person and Detection of Poliovirus in Wastewater—New York, June—August 2022

Polio Found in New York Wastewater as State Urges Vaccinations

Polio is Found in the UK For the First Time in Nearly 40 years. Here’s What It Means

Poliovirus Detected in Sewage from North and East London

Can’t Help Falling in Love with a Vaccine: How Polio Campaign Beat Vaccine Hesitancy

Vaccine-derived Polio Is on the Rise. A New Vaccine Aims to Stop the Spread

Statement of the Thirty-first Polio IHR Emergency Committee

What is Polio?

Did I Get the Polio Vaccine? How to Know If You Are Protected Against the Virus

Polio Detected in New York City Sewage Suggesting Local Circulation of Virus, Health Officials Say

Wastewater Is Trying to Tell Us Something about the Future of COVID, Polio, Monkeypox, and the Next Epidemic to Come

‘Silent’ Spread of Polio in New York Drives CDC to Consider Additional Vaccinations for Some People

Updated Statement on Report of Polio Detection in United States

Scientists Use Thousands of Genetic Markers to Develop Risk Scores for Six Common Diseases: Findings May Have Implications for Clinical Laboratories

Study demonstrates how precision medicine is advancing because of new insights from the use and interpretation of whole-genome sequencing

As part of the Genomic Medicine at Veterans Affairs Study (GenoVA), researchers from Harvard Medical School, Veterans Affairs Boston Healthcare System, and Brigham and Women’s Hospital in Massachusetts used thousands of genetic markers to develop and validate polygenic risk scores (PRS) for six common illnesses. These findings may eventually provide clinical laboratories and anatomic pathology groups with useful biomarkers and diagnostic tests.

The focus of the ongoing GenoVA study is to “determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases measured by time-to-diagnosis of prevalent or incident disease over 24 months,” according to the National Institutes of Health.   

The scientists used data obtained from 36,423 patients enrolled in the Mass General Brigham Biobank. The six diseases they researched were:

The polygenic scores were then tested among 227 healthy adult patients to determine their risk for the six diseases. The researchers found that:

  • 11% of the patients had a high-risk score for atrial fibrillation,
  • 7% for coronary artery disease,
  • 8% for diabetes, and
  • 6% for colorectal cancer.

Among the subjects used for the study:

  • 15% of the men in the study had a high-risk score for prostate cancer, and
  • 13% of the women in the study had a high score for breast cancer. 

The researchers concluded that the implementation of PRS may help improve disease prevention and management and give doctor’s a way to assess a patient’s risk for these conditions. They published their findings in the journal Nature Medicine, titled, “Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow.”

“We have shown that [medical] laboratory assay development and PRS reporting to patients and physicians are feasible … As the performance of PRS continues to improve—particularly for individuals of underrepresented ancestry groups—the implementation processes we describe can serve as generalizable models for laboratories and health systems looking to realize the potential of PRS for improved patient health,” the researchers wrote.

Using PRS in Clinical Decision Support

Polygenetic risk scores examine multiple genetic markers for risk of certain diseases. A calculation based on hundreds or thousands of these genetic markers could help doctors and patients make personalized treatment decisions, a core tenet of precision medicine.

“As a primary care physician myself, I knew that busy physicians were not going to have time to take an entire course on polygenic risk scores. Instead, we wanted to design a lab report and informational resources that succinctly told the doctor and patient what they need to know to make a decision about using a polygenic risk score result in their healthcare,” epidemiologist Jason Vassy, MD, told The Harvard Gazette. Vassy is Associate Professor, Harvard Medical School at VA Boston Healthcare System and one of the authors of the research.

Jason Vassy, MD
“This is another great example of precision medicine,” Jason Vassy, MD (above), Adjunct Assistant Professor, General Internal Medicine at Boston University School of Medicine, told WebMD. “There’s always been a tantalizing idea that someone’s genetic makeup might help tailor preventative medicine and treatment.” Personalized clinical laboratory testing is increasingly becoming based on an individual’s genetics. (Photo copyright: Harvard Medical School.)

Increasing Diversity of Patients in Genomic Research

The team did encounter some challenges during their analysis. Because most existing genomic research was performed on persons of European descent, the risk scores are less accurate among non-European populations. The researchers for this study addressed this limitation by applying additional statistical methods to qualify accurate PRS calculations across multiple racial groups.

“Researchers must continue working to increase the diversity of patients participating in genomics research,” said Matthew Lebo, PhD, Chief Laboratory Director, Laboratory Molecular Medicine, at Mass General Brigham and one of the authors of the study. “In the meantime, we were heartened to see that we could generate and implement valid genetic scores for patients of diverse backgrounds,” he told The Harvard Gazette.

The team hopes the scores may be utilized in the future to help doctors and patients make better decisions regarding preventative care and screenings.

“It’s easy to say that everyone needs a colonoscopy at age 45,” Vassy told WebMD. “But what if you’re such a low risk that you could put it off for longer? We may get to the point where we understand risk so much that someone may not need one at all.”

Future of PRS in Clinical Decision Making

The scientists plan to enroll more than 1,000 patients in a new program and track them for two years to assess how medical professionals use PRS in clinical care. It is feasible that patients who are at high risk for certain diseases may opt for more frequent screenings or take preventative medicines to mitigate their risk.

“Getting to that point will take time,” Vassy added. “But I can see this type of information playing a role in shared decision making between doctor and patient in the near future.”

The team also established resources and educational materials to assist both doctors and patients in using the scores.

“It’s still very early days for precision prevention,” Vassy noted, “but we have shown it is feasible to overcome some of the first barriers to bringing polygenic risk scores into the clinic.”

More research and studies are needed to prove the effectiveness of using PRS tests in clinical care and determine its role in customized treatment plans based on personal genetics. Nevertheless, pathologists and medical scientists will want to follow the GenoVA study.  

“It is probably most helpful to think of polygenic risk scores as a risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease,” Vassy said. “Most diseases have complex, multifactorial etiologies, and a high polygenic risk score is just one piece of the puzzle.”

Pathologists and clinical laboratory managers may want to stay informed as researchers in the GenoVA study tease new useful diagnostic insights from their ongoing study of the whole human genome. Meanwhile, the GenoVA team is moving forward with the 1,000-patient study with the expectation that this new knowledge may enable earlier and more accurate diagnoses of the health conditions that were the focus of the GenoVA study.

JP Schlingman

Related Information:

Genetic Risk Scores Developed for Six Diseases

Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow

What If You Knew Your Unique Risk for Every Disease?

Polygenic Risk Scores May Assist Decision-making in Primary Care

University of Utah and Sloan Kettering Institute Study Sheds Light on How the Body Recognizes “Good” from Bad Bacteria in the Microbiome

Researchers found that early in life intestinal microorganisms “educate” the thymus to develop T cells; findings could lead to improved immune system therapeutics and associated clinical laboratory tests

Researchers at the University of Utah and the Sloan Kettering Institute (SKI)—the experimental research division of the Memorial Sloan Kettering Cancer Center (MSKCC) in New York—have uncovered new insights into how the immune system learns to distinguish between harmful infectious bacteria and “good” bacteria in the microbiome that occupies the gastrointestinal tract.

The researchers published their findings in Nature. They used engineered mice as the test subjects and say the study could lead to a greater understanding of human conditions such as Type 1 and Type 2 diabetes and inflammatory bowel disease (IBD). In turn, this new knowledge could lead to new diagnostic tests for clinical laboratories.

“From the time we are born, our immune system is set up so that it can learn as much as it can to distinguish the good from the bad,” Matthew Bettini, PhD, Associate Professor of Pathology said in a University of Utah news release.

Does Gut Bacteria ‘Educate’ the Immune System?

The researchers were attempting to learn how the body develops T cells specific to intestinal microorganisms. T cells, they noted, are “educated” in the thymus, an organ in the upper chest that is key to the adaptive immune system.

“Humans and their microbiota have coevolved a mutually beneficial relationship in which the human host provides a hospitable environment for the microorganisms and the microbiota provides many advantages for the host, including nutritional benefits and protection from pathogen infection,” they wrote in their study. “Maintaining this relationship requires a careful immune balance to contain commensal microorganisms within the lumen, while limiting inflammatory anti-commensal responses.”

Matthew Bettini, PhD and Gretchen Diehl, PhD

Matthew Bettini, PhD (left), Associate Professor of Pathology at the University of Utah, co-authored the study along with Gretchen Diehl, PhD (right), an immunologist at Sloan Kettering Institute. The team also included researchers from the Baylor College of Medicine in Houston and the Washington University School of Medicine in St. Louis. “Our studies make clear that there is a window in which gut microbiota have access to the immune education process. This opens up possibilities for designing therapeutics that can influence the trajectory of the immune system during this early time point,” Bettini said in the University of Utah news release. (Photo copyright: University of Utah/Sloan Kettering Institute.)

Findings Challenge Earlier Assumptions about Microbiota’s Influence on Immunity

The researchers began by seeding the intestines of mice with segmented filamentous bacteria (SFB), which they described as “one of the few commensal microorganisms for which a microorganism-specific T-cell receptor has been identified.” In addition, SFB-specific T cells can be tracked using a magnetic enrichment technique, they wrote in Nature.

They discovered that in young mice, microbial antigens from the intestines migrated to the thymus, resulting in an expansion of T cells specific to SFB. But they did not see an expansion of T cells in adult mice, suggesting that the process of adapting to microbiota happens early.

“Our study challenges previous assumptions that potential pathogens have no influence on immune cells that are developing in the thymus,” Bettini said in the news release. “Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape which T cells are present happen early in life, they can have a greater impact later in life.”

For example, T cells specific to microbiota can also protect against closely related harmful bacteria, the researchers found. “Mice populated with E. coli at a young age were more than six times as likely to survive a lethal dose of Salmonella later in life,” the news release noted. “The results suggest that building immunity to microbiota also builds protection against harmful bacteria the body has yet to encounter.”

According to the researchers, in addition to protecting against pathogens, “microbiota-specific T cells have pathogenic potential.” For example, “defects in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation that’s responsible for inflammatory bowel disease,” they suggested.

Other Clinical Laboratory Research into the Human Microbiome

The research conducted by the University of Utah, Sloan Kettering Institute, and others, adds to a growing understanding of the human microbiome. For example, in “International Study into Ancient Poop Yields Insight into the Human Microbiome, May Produce Useful Insights for Microbiologists,” Dark Daily reported on an international study of 2000-year-old human feces which suggested that the microbiomes of today’s humans may have been modified by modern phenomena such as processed food and sanitation.

And in “Harvard Medical School Study Finds ‘Staggering’ Amounts of Genetic Diversity in Human Microbiome; Might Be Useful in Diagnostics and Precision Medicine,” Dark Daily reported on a study from Harvard Medical School and Joslin Diabetes Center that unveiled a “staggering microbial gene diversity” in the microbiome and the potential for identification of more-useful biomarkers for disease detection.

And a study from the University of Nebraska-Lincoln and the Ocean Road Cancer Institute in Tanzania raised the possibility that bacteria in the cervical microbiome could lead to new tests for cervical cancer. (See Dark Daily, “University Study Suggests Cervical Microbiome Could Be Used by Medical Laboratories as Biomarker in Determining Women’s Risk for Cervical Cancer.”

All of this suggests the potential in the future “for clinical laboratories and microbiologists to do microbiome testing in support of clinical care,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report. Of course, more research is needed in these areas.

“We believe that our findings may be extended to areas of research where certain bacteria have been found to be either protective or pathogenic for other conditions, such as Type 1 and Type 2 diabetes,” Bettini said in the University of Utah news release. “Now we’re wondering, will this window of bacterial exposure and T cell development also be important in initiating these diseases?”

—Stephen Beale

Related Information

How the Body Builds a Healthy Relationship With ‘Good’ Gut Bacteria

Thymic Development of Gut-Microbiota-Specific T Cells

International Study into Ancient Poop Yields Insight into the Human Microbiome, May Produce Useful Insights for Microbiologists

Harvard Medical School Study Finds ‘Staggering’ Amounts of Genetic Diversity in Human Microbiome; Might Be Useful in Diagnostics and Precision Medicine

University Study Suggests Cervical Microbiome Could Be Used by Medical Laboratories as Biomarker in Determining Women’s Risk for Cervical Cancer

Boston Globe Investigation Finds Many Boston Hospital CEOs Also Sit on Healthcare Company Boards

Cozy relationships between hospital chief executives and healthcare companies they do business with may raise ethical questions

If hospital employees, including pathologists, wonder why their hospital uses a certain company’s products and services it may be because their Chief Executive Officer (CEO) sits on the Board of Directors of the same companies from which the hospital buys products and services. That’s the suggestion in a recent Boston Globe investigative report.

In “Boston’s Hospital Chiefs Moonlight on Corporate Boards at Rates Far Beyond the National Level,” The Boston Globe reported that, in Boston, hospital CEOs at the city’s academic medical centers frequently sit on the boards of healthcare companies with which their hospitals do business. However, because the investigative reporters did not list the healthcare companies which had Boston hospital CEOs as board members, clinical laboratory managers and pathologists cannot determine from the article if their medical laboratories are using products from those same companies.

According to The Globe, five of seven CEOs and Presidents of Boston’s major teaching hospitals also receive compensation for serving as directors of publicly traded companies. And in their roles as corporate board members, hospital CEOs often receive stock in these companies, making the value of their remuneration potentially worth millions of dollars, The Globe reported.

Not Illegal, But Is It Ethical?

The Boston Globe’s investigation noted that such moonlighting, while not unheard of elsewhere in the country, is commonplace in Boston, raising ethical concerns despite conflict-of-interest policies aimed at limiting outside relationships.

“Hospitals in Boston and elsewhere that allow this outside corporate work do so under the terms of conflict-of-interest policies,” The Globe reported. “A Globe review of more than a dozen hospital conflict-of-interest policies across the country found more similarities than differences. Almost all require hospital trustees to approve a hospital chief’s outside board work and consider certain factors, such as the amount of business a company does with the hospital and time required.

“But the policies offer limited evidence about actual practices,” The Globe added. “Trustees typically retain significant discretion over what is permitted or barred, and their deliberations are generally hidden from the public. It is hard to tell if the relative rarity of hospital chiefs in other cities holding outside directorships is because of a lack of interest or opportunity, or is the result of trustees saying no.”

One of the hospital chief executives The Globe’s investigation highlighted was former-Boston Children’s Hospital CEO Sandra Fenwick. While there, The Globe noted, she also held a seat on the board of for-profit telehealth company Teledoc Health, and during her tenure as Children’s CEO, she lobbied Massachusetts legislators for telehealth funding at the start of the COVID-19 pandemic.

Though no laws were broken, some questioned the ethics of such actions. Nevertheless, The Boston Globe wrote that “Debra O’Malley, a spokesperson for Secretary of State William Galvin’s office, said Fenwick’s actions did not appear to violate the law: She is required to disclose in writing to the state that she is a lobbyist for the hospital and the bills she lobbied on, which she did, O’Malley said. That information is publicly available.”

And though The Globe reported that Boston Children’s Hospital had “declined to answer detailed questions about [Fenwick’s] lobbying efforts,” the paper wrote that a hospital spokesperson said, “[Fenwick’s] directorships are publicly disclosed in filings with the Securities and Exchange Commission.”

Fenwick retired from Boston Children’s Hospital in March 2021. The Globe noted that at that time her Teledoc Health stock, which was compensation for her board work, was worth $8.8 million. Additionally, she had been paid $2.7 million annually as CEO of Boston Children’s Hospital.

carl-elliott-md-phd-at-podium
“It does seem like buying influence and it’s hard to imagine what else it would be,” Carl Elliott, MD, PhD (above), Professor in the Center for Bioethics and the Department of Pediatrics at the University of Minnesota told BioPharma Dive. “If you’re actually trying to buy scientific knowledge, then you wouldn’t really be going after CEOs. What they have is power.” (Photo copyright: Boston University.)

Avoiding Conflicts of Interest

Bad optics created by a Boston hospital CEO receiving seven-figure compensation for serving on the board of directors of a publicly traded company is not new. In July 2020, former Brigham and Women’s Hospital President Elizabeth Nabel, MD, resigned from the board of biotech company Moderna (NASDAQ:MRNA) “to alleviate any potential concern about the conduct or the outcome of the COVID-19 vaccine trial when Brigham and Women’s Hospital was identified by NIH as one of the clinical sites for the Phase 3 trial,” a Moderna press release states.

On March 1, 2021, Nabel also stepped down as Brigham and Women’s Hospital president. She then rejoined the Moderna board of directors on March 10, 2021, the press release noted.

In a STAT editorial, titled, “Hospital CEOs, Med School Leaders Shouldn’t Sit on For-Profit Health Care Company Boards,” endocrinologist and former Dean of Harvard Medical School Jeffrey Flier, MD, wrote, “As dean, I vigorously supported the value of robust interactions between faculty and industry to advance innovation and human health, and still do. In my current status as a professor of medicine at Harvard, I serve on several for-profit and not-for-profit boards. I learn from this work, and I believe I am making useful contributions as a board member. But I also believe that the considerations governing such relationships should be judged differently for institutional leaders.”

Flier maintains there are multiple reasons why hospital and medical school leaders should not sit on for-profit boards despite the expertise they bring to the table, including:

  • The time commitment required,
  • The “extraordinary compensation packages” they receive in their full-time jobs,
  • The potential for complicated “business intersections,” and
  • The risks to an “institution’s reputation for integrity.”

“I recommend that hospital CEOs and academic leaders at the level of Deans and Presidents devote their full attention to their well-compensated day jobs and defer positions on the boards of for-profit companies—and the unavoidable conflicts they raise—to the post-leadership phase of their careers,” Flier wrote.

While cozy relationships between hospital and academic medical center leaders and for-profit healthcare companies may not directly impact hospital pathologists and staff, it is worth staying aware of potential conflicts of interest.

Andrea Downing Peck

Related Information:

Boston’s Hospital Chiefs Moonlight on Corporate Boards at Rates Far Beyond the National Level

Elizabeth Nabel Steps Down as President of Brigham and Women’s Hospital to Team Up with Husband’s Biotech Joint–Report

Betsy Nabel, MD, to Step Down as President of Brigham Health

Dr. Elizabeth Nabel Rejoins Moderna’s Board of Directors

Hospital CEOs, Med School Leaders Shouldn’t Sit on For-Profit Health Care Company Boards

Researchers at Harvard’s Massachusetts General Hospital Develop a Non-Invasive Liquid Biopsy Blood Test to Detect and Monitor Common Brain Tumors in Adults

Breakthrough assay a ‘tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors,’ MGH says in an affirmation of a diagnostic technology clinical labs might soon use

In recent years, investors have poured tens of millions of dollars into companies that promised to create non-invasive cancer tests which use liquid biopsy technology. Medical laboratory scientists even watched some of these companies hype their particular liquid biopsy tests before clinical studies generated data demonstrating that these tests produced accurate, reliable, and reproducible results.

For diagnosing cancer, a liquid biopsy test typically uses a blood sample with the goal of finding and identifying circulating tumor cells. Harvard Medical School researchers at Massachusetts General Hospital (MGH) believe they have developed just such a blood test. Their assay utilizes an enhanced form of liquid biopsy to detect and monitor one of the more prevalent types of brain tumor in adults—a glioma—and, according to a Harvard news release, can detect the presence of glioma at a significantly higher “overall sensitivity” than other similar liquid-biopsy tests.

Gliomas start in glia cells contained in the brain or spine. They account for about 30% of all brain and central nervous system tumors and 80% of all malignant brain tumors.

During their study, MGH researchers compared blood samples and tumor biopsy tissues from patients diagnosed with a glioma. They discovered that an assay they developed—a droplet digital polymerase chain reaction (ddPCR) blood test—could detect and monitor two types of telomerase reverse transcriptase (TERT) promoter gene mutations—C228T and C250T. These two gene mutations promote cancer growth and are present in more than 60% of all gliomas. The mutations are also present in 80% of all high-grade gliomas, which are the most aggressive and life-threatening types of the cancer.  

In the press release, instructor in Neurosurgery at MGH and one of the study’s authors, Leonora Balaj, PhD, said, “By ‘supercharging’ our ddPCR assay with novel technical improvements, we showed for the first time that the most prevalent mutation in malignant gliomas can be detected in blood, opening a new landscape for detection and monitoring of the tumors.”

The MGH researchers released their findings in Clinical Cancer Research, a peer-reviewed medical journal devoted to the field of oncology published by the American Association of Cancer Research (AACR). 

Bob Carter, MD, PhD
Bob Carter, MD, PhD (above), is neurosurgical oncologist and Chief of Neurosurgery at MGH, a Professor of Neurosurgery at Harvard Medical School, and one of the study’s authors. In the MGH press release he said, “We envision the future integration of tests like this one into the clinical care of our patients with brain tumors. For example, if a patient has a suspected mass on MRI scanning, we can take a blood sample before the surgery and assess the presence of the tumor signature in the blood and then use this signature as a baseline to monitor as the patient later receives treatment, both to gauge response to the treatment and gain early insight into any potential recurrence.” What Carter describes is precision medicine and could open new diagnostic opportunities for anatomic pathology groups and clinical laboratories. (Photo copyright: Massachusetts General Hospital.)

MGH’s Ten-Fold Improvement over Previous ddPCR Assays

A liquid biopsy is the sampling and analysis of non-solid tissue in the body—primarily blood. MGH’s liquid-biopsy method detects cancer by examining fragments of tumor DNA circulating in the bloodstream. Since the technique is mostly non-invasive, tests can be performed more frequently to track tumors and mutations and monitor treatment progression. Prior to this new method, brain tumors had been difficult to detect using liquid biopsies.

“Liquid biopsy is particularly challenging in brain tumors because mutant DNA is shed into the bloodstream at a much lower level than any other types of tumors,” Balaj said in the press release.

However, MGH’s new ddPCR assay has an overall sensitivity rate of 62.5% and a specificity of 90%, which represents a tenfold improvement over prior assays for TERT mutations in the blood.

And when testing the performance of the ddPCR assay in tumor tissue, the MGH researchers discovered their results were the same as results from a previous independently-performed clinical laboratory assessment of TERT mutations within collected tumor specimens. They also found that their assay could detect TERT mutations when looking at blood plasma samples collected at other facilities.

The researchers believe that their test could be performed in most clinical laboratories and can be utilized to follow the course of disease in cancer patients. The MGH researcher’s goal is to expand and adapt the blood test to diagnose, differentiate, and monitor other types of brain tumors in addition to gliomas.

Of course, more research will be needed before MGH’s new assay can become a vital tool in the fight against disease. However, this type of genetic analysis may soon provide pathologists with new techniques to more accurately diagnose and monitor cancers, and to provide healthcare providers with valuable data regarding which therapies would be the most beneficial for individual patients, a key element of precision medicine. 

—JP Schlingman

Related Information:

Breakthrough Blood Test Developed for Brain Tumors

TERT Promoter Mutation Analysis for Blood-based Diagnosis and Monitoring of Gliomas

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