By Nana O 
Scientists and medics have developed an ultra-rapid method of genetically diagnosing brain tumours that will cut the time it takes to classify them from 6-8 weeks, to as little as two hours — which could improve care for thousands of patients each year in the UK. This groundbreaking advancement, detailed in a new study published today in Neuro-Oncology, heralds a paradigm shift in neuro-oncology, promising to alleviate patient anxiety, expedite critical treatment decisions, and potentially improve survival rates for those battling aggressive forms of the disease.
Developed collaboratively by researchers at the University of Nottingham and clinicians at Nottingham University Hospitals NHS Trust (NUH), the innovative technique leverages cutting-edge nanopore sequencing technology to provide near real-time genetic analysis of brain tumour samples. This significantly reduces the diagnostic bottleneck that has long plagued the traditional pathway, a delay that can have profound consequences for patient outcomes.
From Weeks of Waiting to Hours of Insight: The Nanopore Revolution
The traditional diagnostic process for brain tumours is a protracted and resource-intensive undertaking. Following surgical removal of a tumour sample, it is typically sent to centralized pathology laboratories for extensive genetic analysis. This involves intricate DNA extraction, followed by complex testing to identify specific genetic mutations and abnormalities that are crucial for classifying the tumour type and predicting its behaviour. Historically, obtaining these results could take anywhere from six to eight weeks, and often longer, leaving patients in a state of agonizing uncertainty about their diagnosis and prognosis.
This extended waiting period is not merely an inconvenience; it carries significant clinical implications. The delay can postpone the commencement of essential treatments such as radiotherapy and chemotherapy, which are most effective when initiated promptly after surgery. Furthermore, the psychological toll on patients and their families during this prolonged period of not knowing can be immense, exacerbating an already traumatic experience.
The new method, however, promises to dismantle this lengthy diagnostic timeline. By employing portable nanopore sequencing devices, developed by Oxford Nanopore Technologies, the Nottingham-based team has engineered a system capable of analyzing specific regions of the human genome with unprecedented speed and depth. This technology allows for the rapid sequencing of targeted DNA segments, directly addressing the critical questions needed for tumour classification.
Intraoperative Precision: A New Era for Surgical Decision-Making
A pivotal aspect of this new methodology is its successful implementation during actual surgical procedures. In a series of 50 brain tumour surgeries, the NUH team utilized the rapid sequencing approach to deliver intraoperative diagnoses. The results have been nothing short of remarkable, achieving a 100% success rate in providing diagnostic insights within two hours of sample collection. More impressively, detailed tumour classifications are being generated within minutes of sequencing, with the platform’s continuous sequencing capabilities enabling a comprehensive diagnosis to be finalized within 24 hours.
This intraoperative capability is a potential game-changer for surgical strategy. Dr. Stuart Smith, a Neurosurgeon from the School of Medicine at the University of Nottingham and within NUH, explained the transformative impact. "Traditionally, the process of diagnosing brain tumours has been slow and expensive," Dr. Smith stated. "Now, with this new technology, we can do more for patients because we can get answers so much more quickly, which will have a much bigger influence on clinical decision making, in as little as two hours. Patients find waiting many weeks for results extremely difficult, and this adds to the anxiety and worry at what is already a very difficult time."
He further elaborated on the potential during lengthy surgical procedures: "This type of operation can be quite long, so potentially, a surgeon could be informed during surgery of the accurate diagnosis, which would then impact on the surgical strategy." This means surgeons could potentially make more informed decisions about the extent of tumour resection in real-time, based on the genetic profile of the tumour, potentially leading to more precise and effective surgical interventions.
The Science Behind the Speed: Nanopore Sequencing and ROBIN
The technological backbone of this breakthrough lies in the innovative work of Professor Matt Loose, a biologist from the School of Life Sciences at the University of Nottingham. Professor Loose pioneered a method to sequence specific parts of human DNA at higher depths using portable nanopore sequencing devices. This approach allows for the targeted examination of crucial genomic regions, significantly accelerating the diagnostic process.
The system utilizes Oxford Nanopore Technologies’ PromethION nanopore sequencers, powered by a software tool named ROBIN. This sophisticated system sequences DNA by detecting minute changes in electrical current as single molecules of DNA pass through tiny pores in a membrane. By focusing on specific, diagnostically relevant regions of the genome, rather than sequencing the entire genome, the time required for analysis is drastically reduced.
"When we first were able to sequence an entire human genome in 2018, it took around five labs and six months to do, which obviously isn’t ideal when time is of the essence for a patient," Professor Loose remarked. "This new method now allows us to choose the bits of DNA that we need to look at in order to answer specific questions, such as what type of tumour and how it can be treated. Combined with our later research where we were able to look at relevant parts of the human genome more quickly – then we now have a process where we can use ROBIN to create comprehensive classifications of tumours more quickly."
A key aspect of tumour classification, particularly in brain tumours, is the analysis of DNA methylation patterns. Methylation is an epigenetic modification that plays a crucial role in gene regulation and is a powerful indicator of tumour type and origin. Professor Loose highlighted its importance: "Once we have a sample from a patient, we can now quickly extract the DNA and look at the different properties to give us the information we need. Methylation is the one we are most interested in early on in this instance because that defines the tumour type."
A Daily Challenge: The Scale of Brain Tumour Diagnosis in the UK
The significance of this advancement is underscored by the sheer scale of the challenge it addresses. Every day in the UK, an estimated 34 people are diagnosed with some form of brain tumour, equating to more than 12,000 cases annually. The impact of these diagnoses can be devastating, with the average survival rate for the most aggressive brain cancers often being less than a year.
The traditional diagnostic pathway, as described, begins with an MRI scan to detect the presence of a tumour. Patients then consult with clinicians to discuss potential tumour types. For many, surgery is required to obtain a tissue sample. This sample is then sent for genetic analysis, a process that, until now, has been characterized by significant delays.
Historically, neuropathologists relied heavily on visual examination of tumour cells under a microscope. While this remains a critical component of diagnosis, the advent of molecular and genetic profiling has revolutionized tumour classification in recent years. Tumours are increasingly categorized based on their specific DNA and genetic abnormalities, a process that has been hindered by the technological limitations of traditional sequencing methods.
A Transformative Breakthrough: Expert Reactions and Broader Implications
The medical community has responded with considerable enthusiasm to this groundbreaking development. Dr. Simon Paine, a Consultant Neuropathologist at NUH, described the new method as "a game changer, it really is revolutionary." He further emphasized the dual benefits: "It not only increases the speed at which the results will be available, but the degree of accuracy of the diagnosis as well is incredible."
The implications of this rapid and accurate diagnostic platform extend far beyond the immediate patient benefit. The ability to consolidate multiple, traditionally separate, genetic tests into a single, rapid analysis has significant cost-saving potential. Professor Loose estimates the cost to be around £450 per person, with the potential for further reduction when scaled up. This efficiency is achieved by eliminating the need for four to five separate tests, yielding more comprehensive information from a single, expedited process.
The Brain Tumour Charity, a leading organization dedicated to supporting those affected by brain tumours, has also lauded the advancement. Dr. Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, stated, "The delivery of an accurate diagnosis within hours of surgery will be transformative for all patients, ensuring rapid access to the optimal standard of care and – crucially – removing the uncertainty patients face when having to wait weeks for their diagnosis and prognosis."
Dr. Newman also highlighted the potential for this technology to drive equity in healthcare: "The potential to combine so many separate tests into one and deliver at a localised level is a game-changer for driving equity of access to rapid and accurate molecular diagnosis." The charity is actively involved in exploring the broader applications of this technology, including the BRAIN MATRIX Trial, which aims to match patients with personalized clinical trials across the UK based on their genetic tumour profiles.
The Road Ahead: National Rollout and Future Prospects
The success of this pioneering work at the University of Nottingham and NUH has paved the way for its wider adoption. The team is now actively pursuing plans to roll out this new testing methodology across NHS Trusts throughout the UK. This national implementation could dramatically improve the diagnostic experience for thousands of patients annually, offering them faster answers, more informed treatment decisions, and a reduced period of debilitating uncertainty.
The development represents a significant leap forward in the fight against brain tumours, a disease that continues to pose a formidable challenge to medical science. By harnessing the power of cutting-edge genetic sequencing technology and innovative software, scientists and clinicians have not only accelerated the diagnostic process but have also enhanced its accuracy and cost-effectiveness. This convergence of scientific ingenuity and clinical application offers a beacon of hope for patients and a testament to the relentless pursuit of better healthcare solutions. The ability to provide a comprehensive genetic diagnosis within hours, rather than weeks, marks a profound turning point in the management of brain tumours, promising a future where timely and precise diagnosis is the standard of care.
