11 August 2022
Researchers from the University of Oxford, KTH Royal Institute of Technology, Science for Life Laboratory, and the Karolinska Institutet, Solna, Sweden, have found that individual prostate tumours contain a previously unknown range of genetic variation.
Understanding which cells give rise to which areas of cancer can improve our understanding of how a tumour has grown and developed, including how it has changed genetically, over time. This has been made possible using a new technique called spatial transcriptomics, which allows scientists to see what genetic changes take place without breaking up the tissue they’re looking at. This adds a new dimension which researchers have now used to reveal which cells have mutated and where within the ecosystem of an organ.
Current techniques for studying the genetics of cells within tumours involve taking a sample from the cancerous area and analysing the DNA of those cells. The problem is that many cancers, such as prostate cancer, are three dimensional, which means that any one sample would only give a small snapshot of the tumour.
In a new study published in Nature and funded by Cancer Research UK, the researchers used spatial transcriptomics to create a cross-sectional map of a whole prostate, including areas of healthy and cancerous cells. By grouping cells according to similar genetic identity, they were surprised to see areas of supposedly healthy tissue that already had many of the genetic characteristics of cancer. This finding was surprising because of both the genetic variability within the tissue as well as the large number of cells that
would be considered healthy, but which contained mutations usually identified with cancerous cells.
Alastair Lamb of Oxford’s Nuffield Department of Surgical Sciences, who jointly led the study, said: “Prostate tissue is three-dimensional, and like most organs that can develop cancer we still have much to learn about what cellular changes cause cancer and where it starts. One thing we are fairly confident of is that it starts with genetic mutations.
“We have never had this level of resolution available before, and this new approach revealed some surprising results. For example, we have found that many of the copy number events we previously thought to be linked specifically to cancer are actually already present in benign tissue. This has big implications for diagnosis and also potentially for deciding which bits of a cancer need treating.”
Professor Joakim Lundeberg of KTH Royal Institute of Technology, said: "Mapping thousands of tissue regions in a single experiment is an unprecedented approach to deconvolute the heterogeneity of tumours and their microenvironment. This high-resolution view impacts our way of addressing complex ecosystems such as cancer. The possibility to identify early events is particularly exciting going forward.”
Furthermore, the researchers analysed more than 150,000 regions in three prostates, two breast cancers, some skin, a lymph node and some brain tissue, and developed an algorithm to track groups of cells with similar genetic changes -clones- in their precise location. This approach enabled them to zoom right in from visible tissue through microscopic multi-cellular structures and right into the genes themselves, while keeping hold of the overall landscape of tissue.
Dr Henry Stennett, Research information manager at Cancer Research UK said: "This fascinating research challenges our understanding of how cancer develops. Using cutting-edge technology, our scientists have built an incredibly detailed 3D map of the prostate. Their results show that apparently healthy cells in the body can have the same DNA damage as cancer cells. Working out what stops them from becoming cancerous could help us to detect this disease earlier."
Notes to Editors
The full paper, ‘Spatially resolved clonal copy number alterations in benign and malignant tissue, is published in Nature.
More information on the research can be found in this video: https://vimeo.com/angelsharp/review/713480671/0d2027fcaa
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The Nuffield Department of Surgical Sciences
The Nuffield Department of Surgical Sciences (NDS) at the University of Oxford hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training. We comprise of major surgical specialties, including gastro-intestinal, transplantation, vascular, paediatric, plastic, ear, nose and throat (ENT), neurosurgery, and urology. The research environment in NDS includes a long-established immunology, tolerance and transplantation biology group. It also has well-established groups in bone cancer biology, islet-cell isolation and transplantation, alongside cardiovascular and functional neurosurgical groups, high intensity focused ultrasound and urological oncology. In recent years, the department has expanded in areas of basic cancer research, pathology, bioinformatics and artificial intelligence. NDS is also home to multiple biobanks, a clinical trials centre and a group of research nurses underpinning the research we do in the department. There are over 200 staff in the department who work together to lead discovery, innovation and education in surgical sciences. www.nds.ox.ac.uk
The University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the sixth year running, and 2 in the QS World Rankings 2022. At the heart of this success is our ground-breaking research and innovation.
Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.
Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 200 new companies since 1988. Over a third of these companies have been created in the past three years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs.
KTH Royal Institute of Technology
Since its founding in 1827, KTH Royal Institute of Technology in Stockholm has grown to become one of Europe’s leading technical and engineering universities, as well as a key centre of intellectual talent and innovation. KTH is Sweden’s largest technical research and learning institution and home to students, researchers and faculty from around the world dedicated to advancing knowledge.
As a national hub for molecular biosciences in Sweden, SciLifeLab develops and maintains unique research infrastructure, services and data resources for life science. SciLifeLab coordinates research communities in health and environmental science, recruitment and training of young scientists, and fosters collaboration with industry, health care, public research organizations and international partners. The overall aim of SciLifeLab is to facilitate cutting-edge, multi-disciplinary life science research and promote its translation to the benefit of society.
SciLifeLab is jointly operated by its four founder universities: KTH Royal Institute of Technology, Karolinska Institutet, Stockholm University and Uppsala University. About 200 research groups, 1500 researchers and 40 national infrastructure units are associated with SciLifeLab. The two main research centers are located in Stockholm and Uppsala, but national SciLifeLab units exist at all major Swedish universities.