Scientists from the University of Oxford, KTH Royal Institute of Technology, Science for Life Laboratory, and the Karolinska Institutet, Solna, Sweden, have collaborated and discovered that individual prostate tumours contain a previously unknown range of genetic variation.
Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer and the new research forms part of this attempt to boost medical understanding of this process.
This is an important step in the medical investigation of cancers since understanding which cells give rise to which areas of cancer can improve medical understanding of how a tumour has grown and developed. An important consideration is with how the tumour has changed genetically, over time.
This has been advanced using a new technique called spatial transcriptomics, which allows scientists to see what genetic changes take place without breaking up the tissue they are looking at. This process 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 limitation here 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.
For the new study, researchers used spatial transcriptomics to create a cross-sectional map of a whole prostate, including areas of healthy and cancerous cells. They have shown that 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.
A key finding is that copy number events 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.
Furthermore, the high-resolution views achieved should impact the way of addressing complex ecosystems such as cancer. This is drawn out by analysing more than 150,000 regions in three prostates, two breast cancers, some skin, a lymph node and some brain tissue, and then developing an algorithm to track groups of cells with similar genetic changes. The development appears in the journal Nature, titled “Spatially resolved clonal copy number alterations in benign and malignant tissue.
