A new mapping technique has revealed a surprising genetic variation in prostate tumours, which could lead to “big implications for diagnosis”, according to scientists.
Spatial transcriptomics, which enables scientists to see what genetic changes take place without breaking up the tissue they are examining, was used to reveal which cells have mutated and where within the ecosystem of an organ.
The research team, which involved scientists from the University of Oxford, and teams in Sweden at KTH Royal Institute of Technology, Science for Life Laboratory, and the Karolinska Institutet, created a cross-sectional map of a whole prostate, including areas of healthy and cancerous cells.
After grouping cells according to similar genetic identity, they saw areas of supposedly healthy tissue that already had many of the genetic characteristics of cancer.
Writing in the latest edition of *Nature*, they say this 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, added: "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.”
The research team also 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 in their precise location.
This enabled them to zoom in through microscopic multi-cellular structures and into the genes themselves, while keeping hold of the overall landscape of tissue.
Dr Henry Stennett, research information manager at Cancer Research UK, which funded the study, 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."
Spatially resolved clonal copy number alterations in benign and malignant tissue. *Nature* 9 August 2022
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