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UW Medicine Researchers Identify Blood Cell Genetic Mutations That Can Disrupt Liquid Biopsy Results

The discovery is yet another factor that must be considered when developing a liquid biopsy test clinical laboratories can use to detect cancer

How often do disruptive elements present in Liquid biopsies result in misdiagnoses and unhelpful drug therapies for cancer? Researchers at the University of Washington School of Medicine (UW Medicine) in Seattle wanted to know. And the results of their study provide another useful insight for pathologists about the elements that circulate in human blood which must be understood so that liquid biopsy tests can be developed that are not affected by that factor.

Based on their case series study of 69 men with advanced prostate cancer, the UW Medicine researchers determined that 10% of men have a clonal hematopoiesis of indeterminate potential (CHIP) that can “interfere” with liquid biopsies and cause incorrect reports and unneeded prostate cancer treatment, according to their paper published in the journal JAMA Oncology.

The process of clonal hematopoiesis occurs when hematopoietic stem cells generate blood cells that mimic blood mutations in the same way as hematopoiesis, Labroots explained in “Potential Problems with Liquid Biopsies.” Hence, the word “clonal” in the description. 

The UW Medicine researchers advised testing for “variants in the cell-free DNA (cfDNA)” shed in blood plasma to enable appropriate treatment for people with already diagnosed prostate cancer, noted to a UW Medicine news release.

According to pathologist Colin Pritchard, MD, PhD, Associate Professor of Laboratory Medicine and Pathology at the UW Medicine, who led the research team, “clonal hematopoiesis can interfere with liquid biopsies. For example, mutations in the genes BRCA1, BRCA2, and ATM have been closely linked to cancer development.

“Unfortunately, these same genes are also commonly mutated as a result of clonal hematopoiesis,” he told Labroots. Pritchard is also Head of the Genetics Division of Laboratory Medicine at UW Medicine, Director of Clinical Diagnostics for the Brotman Baty Institute for Precision Medicine, and Co-Director of the Genetics and Solid Tumors Laboratory at the University of Washington Medical Center.

“The good news is that, by looking at the blood cellular compartment, you can tell with pretty good certainty whether something is cancer, or something is hematopoiesis,” he said in the news release.

What Does CHIP Interference Mean to a Clinical Laboratory Blood Test?

In their published study, the UW Medicine researchers stressed the “urgent need to understand cfDNA testing performance and sources of test interferences” in light of recent US Food and Drug Administration (FDA) clearance of two PARP inhibitors (PARPi) for prostate cancer:

“We found that a strikingly high proportion of DNA repair gene variants in the plasma of patients with advanced prostate cancer are attributable to CHIP,” the researchers wrote. “The CHIP variants were strongly correlated with increased age, and even higher than expected by age group.

“The high rate of CHIP may also be influenced by prior exposure to chemotherapy,” they added. “We are concerned that CHIP interference is causing false-positive cfDNA biomarker assessments that may result in patient harm from inappropriate treatment, and delays in delivering alternative effective treatment options.

“Without performing a whole-blood control, seven of 69 patients (10%) would have been misdiagnosed and incorrectly deemed eligible for PARP-inhibitor therapy based on CHIP interference in plasma. In fact, one patient in this series had a BRCA2 CHIP clone that had been previously reported by a commercial laboratory testing company with the recommendation to use a PARPi. To mitigate these risks, cfDNA results should be compared to results from whole-blood control or tumor tissue,” the researchers concluded.

To find the clinically relevant CHIP interference in prostate cancer cfDNA testing, researchers used the UW-OncoPlex assay (developed and clinically available at UW Medicine). The assay is a multiplexed next-generation sequencing panel aimed at detecting mutations in tumor tissues in more than 350 genes, according to the UW Medicine Laboratory and Pathology website. 

“To improve cfDNA assay performance, we developed an approach that simultaneously analyzes plasma and paired whole-blood control samples. Using this paired testing approach, we sought to determine to what degree CHIP interferes with the results of prostate cancer cfDNA testing,” the researchers wrote in JAMA Oncology

Men May Receive Unhelpful Prostate Cancer Drug Therapies

The research team studied test results from 69 men with advanced prostate cancer. They analyzed patients’ plasma cfDNA and whole-blood control samples.

Tumor sequencing enabled detection of germline (cells relating to preceding cells) variants from CHIP clones.

The UW Medicine study suggested CHIP variants “accounted for almost half of the somatic (non-germline) DNA repair mutations” detected by liquid biopsy, according to the news release.

Colin Pritchard, MD, PhD
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“About half the time when the plasma is thought to contain a mutation that would guide therapy with these drugs, it actually contains CHIP variants, not prostate cancer DNA variants. That means that in about half of those tested, a patient could be told that he should be administered a drug that is not indicated to treat to his cancer,” said Colin Pritchard, MD, PhD, pathologist and Associate Professor of Laboratory Medicine and Pathology at UW Medicine in the new release. (Photo copyright: University of Washington School of Medicine.)

Other detailed findings of the UW Medicine Study:

  • CHIP variants of 2% or more were detected in cfDNA from 13 of 69 men.
  • Seven men, or 10%, having advanced prostate cancer “had CHIP variants in DNA repair genes used to determine PARPi candidacy.
  • CHIP variants rose with age: 0% in those 40 to 50; 12.5% in men 51 to 60; 6.3% in those 61 to 70; 20.8% in men 71 to 80; and 71% in men 81 to 90.
  • Whole-blood control made it possible to distinguish prostate cancer variants from CHIP interference variants.

“Men with prostate cancer are at high risk of being misdiagnosed as being eligible for PARPi therapy using current cfDNA tests; assays should use a whole-blood control sample to distinguish CHIP variants from prostate cancer,” the researchers wrote in JAMA Oncology.

Liquid Biopsies Are ‘Here to Stay’

Surgical oncologist William Cance, MD, Chief Medical and Scientific Officer, American Cancer Society (ACS) in Atlanta, recognizes the challenge of tumor biology to liquid biopsies. 

“Genetic abnormalities are only one piece of the puzzle. We need to look comprehensively at tumors for the best therapy, from their metabolic changes and protein signatures in the blood to the epigenetic modifications that may occur, as cancers take hold,” he told Oncology Times. “It’s not just shed DNA in the blood.”

The UW Medicine study demonstrates the importance of understanding how all elements in liquid biopsies interact to affect clinical laboratory test results.

“I think liquid biopsies are here to stay,” Cance told Oncology Times. “They’re all part of precision medicine, tailored to the individual.”

Donna Marie Pocius

Related Information:

Association of Clonal Hematopoiesis in DNA Repair Genes with Prostate Cancer Plasma Cell-free DNA Testing Interference

Potential Problems with Liquid Biopsies

Blood Cell Mutations Confound Prostate Cancer Liquid Biopsy

Pursing and Perfecting Use of Liquid Biopsies in Cancer Early Detection

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

Using Extracellular Vesicles, Researchers Highlight Viability of Liquid Biopsies for Cancer Biomarker Detection in Clinical Laboratories

New studies in UK and at Stanford University Show Lung Cancer Cells Circulating in Blood; Findings Could Make It Possible for Pathologists to Diagnose Cancer with ‘Liquid Biopsies’

Proof of Concept Study Demonstrates Machine Learning and AI Can Identify Cancer Cells Based on pH Levels; May Have Applications in Surgical Pathology

The new method employs a pH sensitive dye and AI algorithms to ‘distinguish between cells originating from normal and cancerous tissue, as well as among different types of cancer’ the researchers said

Might a pH-sensitive dye in tandem with an image analysis solution soon be used to identify cancerous cells within blood samples as well within tissue? Recent research indicates that could be a possibility. If further studies and clinical trials confirm this capability, then anatomic pathologists could gain another valuable tool to use in diagnosing cancers and other types of disease.

Currently, surgical pathologists use a variety of hematoxylin and eosin stains (H/E) to bring out useful features in cells and cell structures. So, staining tissue on glass slides is a common practice. Now, thanks to machine learning and artificial intelligence, anatomic pathologists may soon have a similar tool for spotting cancer cells within both tissue and blood samples.

Researchers at the National University of Singapore (NUS) have developed a method for identifying cancer that uses a pH sensitive dye called bromothymol blue. The dye reacts to various levels of acidity in cancer cells by turning colors. “The pH inside cancer cells tends to be higher than that of healthy cells. This phenomenon occurs at the very early phases of cancer development and becomes amplified as it progresses,” Labroots reported.

In “Machine Learning Based Approach to pH Imaging and Classification of Single Cancer Cells,” published in the journal APL Bioengineering, the NUS researchers wrote, “Here, we leverage a recently developed pH imaging modality and machine learning-based single-cell segmentation and classification to identify different cancer cell lines based on their characteristic intracellular pH. This simple method opens up the potential to perform rapid noninvasive identification of living cancer cells for early cancer diagnosis and further downstream analyses.”

According to an NUS news release, the bromothymol blue dye is “applied onto patients’ cells” being held ex vivo in cell culture dishes. The dye’s color changes depending on the acidity level of the cancer cells it encounters. Microscopic images of the now-visible cancers cells are taken, and a machine-learning algorithm analyzes the images before generating a report for the anatomic pathologist.

The NUS researchers claim the test can provide answers in about half an hour with 95% accuracy, Labroots reported.

“The ability to analyze single cells is one of the holy grails of health innovation for precision medicine or personalized therapy. Our proof-of-concept study demonstrates the potential of our technique to be used as a fast, inexpensive and accurate tool for cancer diagnosis,” said Lim Chwee Teck, PhD, NUS Society Professor and Director of NUS’ Institute for Health Innovation and Technology, in the NUS news release.

Lim Chwee Teck, PhD

The novel technique for differentiating cancer cells from non-cancerous cells being developed at the National University of Singapore (NUS) could eventually become useful in detecting cancer cells in tissue samples, either obtained from tumor biopsies or blood samples. “As the number of cells in these samples can be in millions or even billions, the ability to detect the very few cancer cells among the others will be useful for clinicians,” NUS Society Professor and Director of NUS’ Institute for Health Innovation and Technology, Lim Chwee Teck, PhD (above) told The Straits Times. (Photo copyright: The Straits Times.)

AI Cell Analysis versus Laborious Medical Laboratory Steps

By developing an AI-driven method, Professor Lim and the NUS team sought to improve upon time-consuming techniques for identifying cells that traditionally involve using florescent probes, nanoparticles, and labeling steps, or for cells to be fixed or terminated.

“Unlike other cell analysis techniques, our approach uses simple, inexpensive equipment, and does not require lengthy preparation and sophisticated devices. Using AI, we are able to screen cells faster and accurately,” Professor Lim told Labroots. “Furthermore, we can monitor and analyze living cells without causing any toxicity to the cells or the need to kill them.”

The new technique may have implications for cancer detection in tumor tissue as well as in liquid biopsies.

“We are also exploring the possibility of performing the real-time analysis on circulating cancer cells suspended in blood,” Professor Lim said in the NUS news release. “One potential application for this would be in liquid biopsy where tumor cells that escaped from a primary tumor can be isolated in a minimally-invasive fashion from bodily fluids such as blood.”

Diagnosing Cancer in Real Time

The NUS’ method requires more research and clinical studies before it could become an actual tool for anatomic pathologists and other cancer diagnosticians. Additionally, the NUS researchers acknowledged that the focus on only four cell lines (normal cells, benign breast tumor cells, breast cancer cells, and pancreatic cancer cells) limited their study, as did lack of comparison with conventional florescent pH indicators.

Still, the NUS scientists are already planning more studies to advance their concept to different stages of cell malignancy. They envision a “real-time” version of the technique to enable recognition of cells and fast separation of those that need to be referred to clinical laboratories for molecular testing and/or genetic sequencing.

Medical laboratory leaders may want to follow the NUS study. An inexpensive AI-driven method that can accurately detect and classify cancer cells based on pH within the cells is provocative and may be eventually become integrated with other cancer diagnostics.

Donna Marie Pocius

Related Information

Machine Learning-Based Approach to pH Imaging and Classification of Single Cancer Cells

Machine Learning Can Identify Cancerous Cells by Their Acidity

NUS Researchers Harness AI to Identify Cancer Cells by Their Acidity: Novel Technique Paves Way for Faster, Inexpensive, and Accurate Cancer Diagnosis

AI Test Distinguishes Cancer Cells from Healthy Ones Based on Acidity Levels

Researchers Use AI to Identify the pH of Cancer Cells

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

University Researchers Develop Microfluidic Device That Partitions Cancer Cells According to Size in Effort to Create a Useful Liquid Biopsy Method

Could a fast, cheap, and accurate liquid biopsy diagnostic cancer test soon be available to clinical laboratories and anatomic pathology groups?

What if medical laboratories worldwide could perform a simple liquid biopsy diagnostic test that detected cancer in its various forms? Such a test, if affordable and accurate, would be a boon to histopathology and clinical pathology laboratories. Until now, though, such a test has proven to be elusive. But, researchers at the University of Illinois at Chicago (UIC) and Queensland University of Technology (QUT) in Australia think they may have such a technology in hand.

The researchers unveiled a diagnostic device that uses microfluidic technology to identify cell types in blood by their size. The device also “can isolate individual cancer cells from patient blood samples,” according to a news release.

The ability to isolate circulating tumor cells could enable clinical laboratories to perform diagnostic cancer tests on liquid biopsies and blood samples. Dark Daily reported on various studies involving liquid biopsies—an alternative to invasive and costly cancer diagnostic procedures, such as surgery and tissue biopsies—in previous e-briefings.

The new device differs from other microfluidic technologies that rely on biomarkers to attach to tumor cells (aka, affinity separation), New Atlas reported. Papautsky co-authored a research paper on their findings published in Nature: Microsystems and Nanoengineering.

“This new microfluidics chip lets us separate cancer cells from whole blood or minimally diluted blood. Our device is cheap and doesn’t require much specimen preparation or dilution, making it fast and easy-to-use,” said Ian Papautsky, PhD, Professor of Bioengineering at University of Illinois at Chicago, in the news release. He is shown above with members of the Papautsky Lab, which has been developing “microfluidic systems and point- of-care sensors for public health applications.” (Photo copyright: University of Illinois at Chicago.)

Searching for ‘Purity’

The UIC and QUT researchers were motivated by the information-rich nature of circulating tumor cells. They also saw opportunity for escalated “purity” in results, as compared to past studies.

In the paper, they acknowledged the work of other scientists who deployed microfluidic technology affinity-based methods to differentiate tumor cells in blood. Past studies (including previous work by the authors) also explored tumor cells based on size and difference from white blood cells.

“While many emerging systems have been tested using patient samples, they share a common shortcoming: their purity remains to be significantly improved. High purity is in strong demand for circulating tumor cell enumeration, molecular characterization, and functional assays with less background intervention from white blood cells,” the authors wrote in their paper.

How the Device Works

The scientists say their system leverages “size-dependent inertial migration” of cells. According to the news release:

  • Blood passes through “microchannels” formed in plastic in the device;
  • “Inertial migration and shear-induced diffusion” separate cancer cells from blood;
  • Tiny differences in size determine a cell’s attraction to a location; and
  • Cells separate to column locations as the liquid moves.

In other words, the device works as a filter sorting out, in blood samples, the circulating tumor cells based on their unique size, New Atlas explained.

93% of Cancer Cells Recovered by Device

When the researchers tested their new device:

  • Researchers placed 10 small-cell-lung cancer cells into five-milliliter samples of healthy blood;
  • The blood was then flowed through the device; and
  • 93% of the cancer cells were recovered.

“A 7.5 milliliter tube of blood, which is typical volume for a blood draw, might have 10 cancer cells and 35- to 40-billion blood cells. So, we are really looking for a needle in a haystack,” Papautsky stated in the news release.

The graphic above illustrates how, in the lab, the microfluidic device enabled the researchers to separate out cancer cells in six of the eight lung cancer samples they studied. (Graphic copyright: Ian Papautsky, PhD/University of Illinois at Chicago/New Atlas.)

“We report on a novel multi-flow microfluidic system for the separation of circulating tumor cells with high purity. The microchannel takes advantage of inertial migration of cells. The lateral migration of cells strongly depends on cell size in our microchannel, and label-free separation of circulating tumor cells from white blood cells is thus achieved without sophisticated sample predation steps and external controls required by affinity-based and active approaches,” the researchers wrote in their paper.

The device could one day aid physicians in precision medicine and the development of targeted treatment plans for patients, reported Genetic Engineering and Biotechnology News.

Other Microfluidic Diagnostic Devices

The researchers plan wider trials and the addition of biomarkers to enable cancer DNA detection, New Atlas reported, which described the UIC/QUT study as part of a “new wave of diagnostics.”

Another novel liquid biopsy approach to cancer detection is under development at the University of Queensland. It involves a unique nano-scale DNA signature that appeared in breast cancer and other cancer studies. (See, “University of Queensland Researches May Have Found a Universal Biomarker That Identifies Cancer in Various Human Cells in Just 10 Minutes!Dark Daily, May 20, 2019.)

And researchers developed a “labyrinth” label-free microfluidic device that enabled white blood cells and circulating tumor cells to separate during a study at the University of Michigan. (See, “University of Michigan Researchers Use ‘Labyrinth’ Chip Design in Clinical Trial to Capture Circulating Tumor Cells of Different Cancer Types,” Dark Daily, February 2, 2018.)

With so much focus on liquid biopsy research, it may be possible for medical laboratories to one day not only diagnose cancer through blood tests, but also to find the disease earlier and in a more precise way than with traditional tissue sample analysis.

—Donna Marie Pocius

Related Information:

New Microfluidic Device Can Detect Cancer Cells in Blood

Microfluidic Device Promises Cheap and Fast Detection of Cancer Cells in Blood

Isolation of Circulating Tumor Cells in Non-Small-Lung Cancer Patients Using a Multi-Flow Microfluidic Channel

Liquid Biopsies Become Cheap and Easy with New Microfluidic Device

University of Queensland Researchers May Have Found a Universal Biomarker that Identifies Cancer in Various Human Cells in Just 10 Minutes

University of Michigan Researchers Use Labyrinth Chip Design in Clinical Trial to Capture Circulating Tumor Cells of Different Cancer Types

Dark Daily: Liquid Biopsy

University of Queensland Researches May Have Found a Universal Biomarker That Identifies Cancer in Various Human Cells in Just 10 Minutes!

This research could lead to a useful liquid biopsy test that would be a powerful new tool for clinical laboratories and anatomic pathologists

Cancer researchers have long sought the Holy Grail of diagnostics—a single biomarker that can quickly detect cancer from blood or biopsied tissue. Now, researchers in Australia may have found that treasure. And the preliminary diagnostic test they have developed reportedly can return results in just 10 minutes with 90% accuracy.

In a news release, University of Queensland researchers discussed identifying a “simple signature” that was common to all forms of cancer, but which would stand out among healthy cells. This development will be of interest to both surgical pathologists and clinical laboratory managers. Many researchers looking for cancer markers in blood are using the term “liquid biopsies” to describe assays they hope to develop which would be less invasive than a tissue biopsy.

“This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal, and lymphoma,” said Abu Sina, PhD, Postdoctoral Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), in the news release.

“We designed a simple test using gold nanoparticles that instantly change color to determine if the three-dimensional nanostructures of cancer DNA are present,’ said Matt Trau, PhD, Professor of Chemistry at the University of Queensland, and Deputy Director and Co-Founder of UQ’s AIBN, in the news release.

The team’s test is preliminary, and more research is needed before it will be ready for Australia’s histopathology laboratories (anatomic pathology labs in the US). Still, UQ’s research is the latest example of how increased knowledge of DNA is making it possible for researchers to identify new biomarkers for cancer and other diseases.

“We certainly don’t know yet whether it’s the holy grail for all cancer diagnostics, but it looks really interesting as an incredibly simple universal marker of cancer, and as an accessible and inexpensive technology that doesn’t require complicated lab-based equipment like DNA sequencing,” Trau added.

Such a diagnostic test would be a boon to clinical laboratories and anatomic pathology groups involved in cancer diagnosis and the development of precision medicine treatments.

One Test, 90% Accuracy, Many Cancers

The UQ researchers published their study in the journal Nature Communications. In it, they noted that “Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as ‘Methylscape’ is displayed by most cancer types, thus may serve as a universal cancer biomarker.”

While methyl patterning is not new, the UQ researchers say they were the first to note the effects of methyl pattern in a particular solution—water. With the aid of transmission electron microscopy, the scientists saw DNA fragments in three-dimensional structures in the water. But they did not observe the signature in normal tissues in water.

Methylation are marks that indicate whether pieces of DNA should be read,” Dino DiCarlo, PhD, Professor in the Department of Bioengineering and Biomedical Engineering, University of California Los Angeles (UCLA) and Director of Cancer Nanotechnology at UCLA’s Jonsson Comprehensive Cancer Center, told USA Today.


“To date, most research has focused on the biological consequences of DNA Methylscape changes, whereas its impact on DNA physicochemical properties remains unexplored,” UQ scientists Matt Trau, PhD (left), Abu Sina, PhD (center), and Laura Carrascosa (right), wrote in their study. “We exploit these Methylscape differences to develop simple, highly sensitive, and selective electrochemical or colorimetric one-step assays for the detection of cancer.” (Photo copyright: University of Queensland.)

Their test averaged 90% accuracy during the testing of 200 human cancer samples. Furthermore, the researchers found the DNA structure to be the same in breast, prostate, and bowel cancers, as well as lymphomas, noted The Conversation.

“We find that DNA polymeric behavior is strongly affected by differential patterning of methylcytosine leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes,” the researchers wrote in NatureCommunications.“We exploit these methylscape differences to develop simple, highly sensitive, and selective electrochemical or one-step assays for detection of cancer.”

Next Steps for the “Gold Test”

“This approach represents an exciting step forward in detecting tumor DNA in blood samples and opens up the possibility of a generalized blood-based test to detect cancer, Ged Brady, PhD, Cancer Research UK Manchester Institute, told The Oxford Scientist. “Further clinical studies are required to evaluate the full clinic potential of the method.”

Researchers said the next step is a larger clinical study to explore just how fast cancer can be detected. They expressed interest in finding different cancers in body fluids and at various stages. Another opportunity they envision is to use the cancer assay with a mobile device.

DiCarlo told USA Today that such a mobile test could be helpful to clinicians needing fast answers for people in rural areas. However, he’s also concerned about false positives. “You don’t expect all tumors to have the same methylation pattern because there’s so many different ways that cancer can develop,” he told USA Today. “There are some pieces that don’t exactly align logically.”

The UQ researchers have produced an intriguing study that differs from other liquid biopsy papers covered by Dark Daily. While their test may need to be used in combination with other diagnostic tests—MRI, mammography, etc.—it has the potential to one day be used by clinical laboratories to quickly reveal diverse types of cancers.  

—Donna Marie Pocius

Related Information:

Nano-Signature Discovery Could Revolutionize Cancer Diagnosis

Epigentically Reprogrammed Methylation Landscape Drives the DNA Self-Assembly and Serves as a Universal Cancer Biomarker

One Test to Diagnose Them All: Researchers Exploit Cancers’ Unique DNA Signature

Cancer Researchers in Australia Develop Universal Blood Test

Universal 10-Minute Cancer Test in Sight

A 10-Minute, Universal Blood Test for Cancer

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