A groundbreaking advancement in the rapid genetic diagnosis of brain tumours has emerged from an innovative collaboration between scientists and clinicians at the University of Nottingham and Nottingham University Hospitals NHS Trust (NUH). This pioneering technique promises to reduce the traditionally lengthy diagnostic timeline—from six to eight weeks down to an astonishingly swift two hours—offering profound implications for patient outcomes and clinical decision-making. The development of this ultra-rapid diagnostic method stands to revolutionize the current approach to brain tumour care, potentially benefiting thousands of patients within the UK annually.
The core of this advancement lies in a novel sequencing platform and analytical software that enable near-instantaneous genetic profiling of tumours during surgery. Researchers conducted intraoperative testing on fifty brain tumour surgeries, employing this new technique with remarkable success. The results were impressively delivered in under two hours, providing crucial tumour classifications within mere minutes of sequencing initiation. Furthermore, the methodology supports continuous sequencing and data integration, allowing comprehensive diagnostic information to be fully consolidated within 24 hours of surgery, a stark contrast to the protracted timelines of conventional diagnostics.
Brain tumours present a challenging clinical problem demanding complex genetic tests for accurate subtype classification and prognostication. Presently, tumour samples must be sent to centralized laboratories for DNA analysis, a process burdened by substantial delays. These delays extend the window before patients receive definitive diagnoses, thereby postponing the commencement of critical therapies such as radiotherapy and chemotherapy. For patients and families, this extended waiting period is fraught with anxiety and emotional distress, compounding the already difficult journey of dealing with a serious neurological condition.
Dr. Stuart Smith, a neurosurgeon affiliated with the University of Nottingham’s School of Medicine and NUH, highlights the transformative potential of the technology. He explains that genetic diagnosis previously required weeks to complete, hampering timely clinical interventions. With this new method, diagnostic answers can be obtained while the patient remains in surgery, allowing surgeons to tailor operative strategies dynamically according to accurate tumour subtype data. This capability not only enhances surgical precision but also provides immediate, life-changing information to patients in a timely manner.
Traditional diagnostic pathways typically begin with imaging studies such as MRI to identify tumour presence, followed by discussions between clinicians and patients regarding the probable tumour type. Surgical intervention to procure tissue samples remains essential for definitive diagnosis. Historically, neuropathologists relied heavily on microscopic inspection of tumour cells, a method limited by its subjective nature and prolonged turnaround times. Advances in molecular pathology have shifted the focus toward DNA and epigenetic changes within tumours—critical markers that define tumour subgroups and guide therapy—although these too have been constrained by the slow pace of genomic technologies.
The innovation unveiled by the Nottingham team centers on selective nanopore DNA sequencing, a technology deployed via portable Oxford Nanopore devices. Spearheaded by Professor Matt Loose from the School of Life Sciences, this approach focuses sequencing efforts on key genomic regions, allowing for high-depth analysis where it matters most. By concurrently sequencing multiple DNA regions, the platform accelerates data acquisition dramatically, enabling rapid interpretation of complex methylation patterns—a prominent hallmark used to classify brain tumours accurately.
The sequencing instrument, named ROBIN, is integral to this breakthrough. Utilizing the P2 PromethION nanopore sequencer, ROBIN detects electrical current fluctuations as individual DNA molecules thread through nanopores embedded in a membrane. These subtle changes are translated into sequence data in real-time, allowing the identification of specific methylation signatures that characterize tumour identity. Professor Loose recalls the monumental challenges of early human genome sequencing efforts, which required numerous laboratories and half a year to complete. The compact, portable nature of the current technology permits streamlined, rapid, and targeted genomic interrogation tailored to clinical needs.
Once a surgical sample is obtained, it undergoes DNA extraction in the pathology laboratory before being fed into the sequencing workflow. Dr. Simon Paine, Consultant Neuropathologist at NUH, emphasizes the revolutionary nature of this new diagnostic approach—not only does it drastically reduce wait times, but it also significantly enhances the accuracy of tumour classification compared to existing standards. This heightened precision aids in determining prognosis more reliably and optimizing treatment regimens accordingly.
Cost considerations are equally compelling. Professor Loose indicates that the overall expense per patient using this new method is approximately £450, a figure that is expected to decrease with wider adoption and scaling. The consolidation of multiple conventional tests into a single comprehensive assay obviates the need for repeated or sequential analyses, thus delivering economic and logistical efficiencies alongside clinical benefits. Most importantly, patients gain timely access to actionable data, facilitating earlier intervention and improved clinical outcomes.
The impact of swift and precise diagnostics extends beyond the operating room. Dr. Simon Newman, Chief Scientific Officer at The Brain Tumour Charity, underscores the transformative effect such technology has on patient care pathways. Rapid diagnosis not only improves equitable access to standard-of-care treatments across diverse healthcare settings but also lays the groundwork for personalized clinical trial enrollment, as seen in initiatives like the BRAIN MATRIX Trial. This integration could accelerate therapeutic innovation and offer hope to patients facing these devastating malignancies.
From a patient perspective, the difference is monumental. Charles Trigg, a 45-year-old diagnosed with stage 4 glioblastoma, attests to the value of receiving genetic test results much sooner than the traditional eight-week wait. For him, the timeliness of this information offers a form of empowerment, even amid adverse circumstances. Early knowledge imparts a clearer understanding of prognosis and treatment options, enabling patients and their caregivers to make informed decisions and emotionally prepare for what lies ahead, ultimately easing the psychological burden associated with uncertainty.
The advent of this unified nanopore-based methylome classification tool represents a quantum leap in neuro-oncological diagnostics. By harnessing cutting-edge sequencing technology, refined bioinformatics, and integrated clinical workflows, the University of Nottingham and NUH team have delivered a practical solution that fundamentally shifts paradigms in brain tumour management. As the method is progressively rolled out across NHS Trusts, it is poised to become an indispensable component of personalized brain cancer care, promising enhanced survival chances and improved quality of life for thousands of patients each year.
Subject of Research: People
Article Title: ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis
News Publication Date: 21-May-2025
Web References:
DOI link
Keywords:
Human health, Diseases and disorders, Brain cancer, Glioblastomas
