Pathologists and clinical laboratories have an opportunity to help create newborn rWGS programs in their parent hospitals and health systems
Diagnosing disease in infants is particularly difficult using typical clinical laboratory testing and modalities. Thus, the use of rapid Whole Genome Sequencing (rWGS) is gaining acceptance when such a procedure is deemed “medically appropriate” based on the child’s symptoms.
In “Whole Genome Sequencing for Newborns Gains Favor,” Robert Michel, Editor-in-Chief of Dark Daily’s sister publication The Dark Report wrote, “Evidence is swiftly accumulating that use of rapid Whole Genome Sequencing for certain children in NICUs can enable diagnostic insights that guide effective interventions. Further, these pilot rWGS programs in children’s hospitals are showing a solid return on investment because of improved care. It is predicted that more hospitals may soon offer rWGS.”
Conducted at Tufts Medical Center in Boston, the researchers found that “Whole genome tests are nearly twice as good as narrower tests at unearthing genetic abnormalities that can cause disease in infants—the study found 49% of abnormalities, compared to 27% with more commonly used tests targeting particular types of genetic diseases,” the Associate Press reported.
The AP story follows the medical journey of a now 4-year-old who was diagnosed with a rare bleeding disorder. The nearly fatal condition was only caught because broad genetic testing found she suffered from factor XIII deficiency, a blood disorder characterized by the inability to clot properly.
“I’ve been doing clinical trials of babies for over 40 years,” neonatologist Jonathan Davis, MD (above), Chief, Division of Newborn Medicine at Tufts Children’s Hospital at Tufts Medical Center and Professor of Pediatrics, Tufts University School of Medicine, told the AP. “It’s not often that you can do something that you feel is going to really change the world and change clinical practice for everyone.” Clinical laboratories that work with oncologists to treat children suffering from cancer will understand Davis’ enthusiasm. (Photo copyright: Tufts Medicine.)
Incorporating Rapid Whole Genome Sequencing into Infant Care
Genetic diseases are responsible for 41% of infant deaths, according to a Rady Children’s Institute press release, which goes on to say the usage of rWGS may significantly improve the odds for infants born with genetic disorders.
“Broad use of genomic sequencing during the first year of life could have a much greater impact on infant mortality than was recognized hitherto,” said Stephen Kingsmore MD, President/CEO, Rady Children’s Institute for Genomic Medicine, which was one of the additional study sites for the Tufts Medicine researchers.
Genetic testing is already used to predict infant health outcomes, but the Tufts study highlights further developments that could improve the process. Prenatal genetic testing can be utilized both through carrier testing to determine any potential genetic red flags in the parents, and during prenatal screening and diagnostic testing of the fetus.
When an infant presents symptoms after birth, rWGS can then be implemented to cast a broad net to determine the best course of treatment.
According to ScienceDaily, the Tufts study found rWGS “to be nearly twice as effective as a targeted gene sequencing test at identifying abnormalities responsible for genetic disorders in newborns and infants.”
However, the rWGS tests took an average of six days to come back, whereas the targeted tests took only four days, ScienceDaily reported. Also, there is not full consensus on whether a certain gene abnormality is actually the cause of a specific genetic disorder.
“Many neonatologists and geneticists use genome sequencing panels, but it’s clear there are a variety of different approaches and a lack of consensus among geneticists on the causes of a specific patient’s medical disorder,” Jill Maron, MD, Vice Chair of Pediatric Research, Tufts Medical Center, and a co-principal investigator of the Tufts study, told Science Daily.
rWGS Costs versus Return on Investment
Some also question the upfront cost of genetic testing. It can be high, but it’s coming down and Maron stresses the importance of the tests.
“Genome sequencing can be costly, but in this targeted, at-risk population, it proves to be highly informative. We are supportive of ongoing efforts to see these tests covered by insurance,” she told ScienceDaily.
Each of the doctors associated with the Tufts study emphasized the importance of this testing and the good that can be done for this vulnerable group. The potential value to the children, they say, far outweighs the drawbacks of the testing.
“This study provides further evidence that genetic disorders are common among newborns and infants,” Kingsmore told ScienceDaily, “The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population.”
For clinical laboratories, there is also good news about reimbursement for rWGS. In a story published last fall KFF Health News wrote, “Since 2021, eight state Medicaid programs have added rapid whole-genome sequencing to their coverage or will soon cover it, according to GeneDX, a provider of the test. That includes Florida … The test is also under consideration for coverage in Georgia, Massachusetts, New York, and North Carolina, according to the nonprofit Rady Children’s Institute for Genomic Medicine, another major provider of the test.”
“Collectively, these developments are encouraging children’s hospitals, academic centers, and tertiary care centers to look at establishing their own rWGS programs,” wrote Michel in The Dark Report. “In settings where this is appropriate, hospital and health system-based clinical laboratories have an opportunity to take an active role in helping jump start a newborn rWGS program in their institutions.”
Pathologists should continue to monitor rWGS, as well as prenatal and carrier testing, to have a full awareness of its growing use in infant and young child cancer screening.
Though still in trials, early results show tests may be more accurate than traditional clinical laboratory tests for detecting prostate cancer
Within weeks of each other, different research teams in the US and UK published findings of their respective efforts to develop a better, more accurate clinical laboratory prostate cancer test. With cancer being a leading cause of death among men—second only to heart disease according to the Centers for Disease Control and Prevention (CDC)—new diagnostics to identify prostate cancer would be a boon to precision medicine treatments for the deadly disease and could save many lives.
Thus, these are two different pathways toward the goal of achieving earlier, more accurate diagnosis of prostate cancer, the holy grail of prostate cancer diagnosis.
“There is currently no single test for prostate cancer, but PSA blood tests are among the most used, alongside physical examinations, MRI scans, and biopsies,” said Dmitry Pshezhetskiy, PhD (above), Professorial Research Fellow at University of East Anglia and one of the authors of the UEA study. “However, PSA blood tests are not routinely used to screen for prostate cancer, as results can be unreliable. Only about a quarter of people who have a prostate biopsy due to an elevated PSA level are found to have prostate cancer. There has therefore been a drive to create a new blood test with greater accuracy.” With the completion of the US and UK studies, clinical laboratories may soon have a new diagnostic test for prostate cancer. (Photo copyright: University of East Anglia.)
East Anglia’s Research into a More Accurate Blood Test
Scientists at the University of East Anglia (UEA) worked with researchers from Imperial College in London, Imperial College NHS Trust, and Oxford BioDynamics to develop a new precision medicine blood test that can detect prostate cancer with greater accuracy than current methods.
The researchers evaluated their test in a pilot study involving 147 patients. They found their testing method had a 94% accuracy rate, which is higher than that of PSA testing alone. They discovered their test significantly improved the overall detection of prostate cancer in men who are at risk for the disease.
“When tested in the context of screening a population at risk, the PSE test yields a rapid and minimally invasive prostate cancer diagnosis with impressive performance,” Dmitry Pshezhetskiy, PhD, Professorial Research Fellow at UEA and one of the authors of the study told Science Daily. “This suggests a real benefit for both diagnostic and screening purposes.”
The UK scientists hope their test can eventually be used in everyday clinical practice as there is a need for a highly accurate method for prostate cancer screening that does not subject patients to unnecessary, costly, invasive procedures.
Cedars-Sinai’s Research into Nanotechnology Cancer Testing
Researchers from Cedars-Sinai Cancer took a different approach to diagnosing prostate cancer by developing a nanotechnology-based liquid biopsy test that detects the disease even in microscopic amounts.
Their test isolates and identifies extracellular vesicles (EVs) from blood samples. EVs are microscopic non-reproducing protein and genetic material shed by all cells. Cedars-Sinai’s EV Digital Scoring Assay accurately extracts EVs from blood and analyzes them faster than similar currently available tests.
“This research will revolutionize the liquid biopsy in prostate cancer,” said oncologist Edwin Posadas, MD, Medical Director of the Urologic Oncology Program and co-director of the Experimental Therapeutics Program in Cedars-Sinai Cancer in a press release. “The test is fast, minimally invasive and cost-effective, and opens up a new suite of tools that will help us optimize treatment and quality of life for prostate cancer patients.”
The researchers tested blood samples from 40 patients with prostate cancer. They found that their EV test could distinguish between cancer localized to the prostate and cancer that has spread to other parts of the body.
Microscopic cancer deposits, called micrometastases, are not always detectable, even with advanced imaging methods. When these deposits spread outside the prostate area, focused radiation cannot prevent further progression of the disease. Thus, the ability to identify cancer by locale within the body could lead to new precision medicine treatments for the illness.
“[The EV Digital Scoring Assay] would allow many patients to avoid the potential harms of radiation that isn’t targeting their disease, and instead receive systemic therapy that could slow disease progression,” Posadas explained.
Other Clinical Laboratory Tests for Prostate Cancer Under Development
According to the American Cancer Society, the number of prostate cancer cases is increasing. One out of eight men will be diagnosed with the illness during his lifetime. Thus, developers have been working on clinical laboratory tests to accurately detect the disease and save lives for some time.
In “University of East Anglia Researchers Develop Non-Invasive Prostate Cancer Urine Test,” Dark Daily reported on a urine test also developed by scientists at the University of East Anglia that clinical laboratories can use to not only accurately diagnose prostate cancer but also determine whether it is an aggressive form of the disease.
And in “UPMC Researchers Develop Artificial Intelligence Algorithm That Detects Prostate Cancer with ‘Near Perfect Accuracy’ in Effort to Improve How Pathologists Diagnose Cancer ,” we outlined how researchers at the University of Pittsburgh Medical Center (UPMC) working with Ibex Medical Analytics in Israel had developed an artificial intelligence (AI) algorithm for digital pathology that can accurately diagnose prostate cancer. In the initial study, the algorithm—dubbed the Galen Prostate AI platform—accurately detected prostate cancer with 98% sensitivity and 97% specificity.
More research and clinical trials are needed before the new US and UK prostate cancer testing methods will be ready to be used in clinical settings. But it’s clear that ongoing research may soon produce new clinical laboratory tests and diagnostics for prostate cancer that will steer treatment options and allow for better patient outcomes.
U.S. Patent and Trademark Office will hold hearings to determine whether University of California Berkeley, or Broad Institute of Harvard and MIT, should receive patents for new genomic engineering technique
In the race to master gene-editing in ways that will advance genetic medicine and patient care, one of the hottest technologies is CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. But now a patent fight has the potential to complicate how pathologists and other scientists use this exciting technology.
This dispute over the CRISPR patent—a tool that has been hailed as one of the biggest biotech breakthroughs of the decade—will likely be settled in the coming months by the United States Patent and Trademark Office (USPTO).
The USPTO will be reviewing key patents awarded for what is called CRISPR/Cas9. The technology is already generating novel therapies for diseases, which should create new opportunities for pathologists and medical laboratories. (more…)
This technology has potential to create a demand for pathologists to do genetic analysis as a companion diagnostic in support of physicians treating patients with gene-editing proteins
Researchers at Harvard University have demonstrated a new method to deliver gene-editing proteins into cells. This breakthrough could eventually trigger a demand for pathologists to do genetic analysis as the companion diagnostic needed to help clinicians select appropriate gene-editing therapies for their patients.
Of course, it will be several years before such a scenario is feasible. The related example are the companion diagnostic tests that clinical laboratories perform to guide a physician’s decision on an appropriate therapeutic drug. Continued development of gene-editing therapies has the potential to increase the need for pathologists and medical laboratory scientists to do genetic analysis as a companion diagnostic for patients who would benefit from a gene-editing therapy.
The Harvard University researchers used commercially available cationic lipids to deliver genome-editing proteins into cells. The system works on living animals and humans, and the technology enables scientists to precisely and easily change DNA sequences at exact locations. The full study was outlined in an October Nature Biotechnology article. (more…)
Radiology and pathology associations are supporting a new bill in Congress to address self-referrals made by urologists
Criticism is mounting against urologists who refer their patients to radiation providers in which they have an ownership relationship. This criticism is strikingly similar to concerns that pathologists and others have expressed about situations where urologists refer their patients to anatomic pathology laboratories in which they have an ownership relationship.
Study about Radiation Therapy Referrals Published in NEJM(more…)
