Novel model shows how genomic instability arises in histologically benign tissue

Novel model shows how genomic instability arises in histologically benign tissue

Understanding which cells give rise to which areas of cancer can improve our understanding of how a tumor grew and developed, including how it changed genetically over time. This was made possible by a new technique called spatial transcriptomics, which allows scientists to see what genetic changes are taking place without breaking down the tissue under consideration. This adds a new dimension that researchers have now used to reveal which cells have mutated and where in an organ's ecosystem.

Current techniques for studying the genetics of cells in tumors include taking a sample from the cancerous area and analyzing the DNA of those cells. The problem is that many cancers, like prostate cancer, are three-dimensional, meaning that each individual sample would only provide a small snapshot of the tumor.

In a new study published in Nature and funded by Cancer Research UK, researchers used spatial transcriptomics to create a cross-sectional map of an entire prostate, including areas of healthy and cancerous cells. By grouping cells by similar genetic identity, they were surprised to see areas of supposedly healthy tissue that already had many of the genetic hallmarks of cancer. This finding was surprising both because of the genetic variability within the tissue and because of the large number of cells that would be considered healthy but contained mutations normally identified with cancer cells.

Prostate tissue is three-dimensional, and like most organs that can develop cancer, we still have a lot to learn about what cellular changes cause cancer and where it starts. We’re pretty sure it starts with genetic mutations.”

Alastair Lamb, Nuffield Department of Surgical Sciences, University of Oxford

"We have never had this level of resolution available before, and this new approach revealed some surprising results. For example, we found that many of the copy number events that we previously thought were specifically associated with cancer are actually already present in benign tissue. This has major implications for diagnosis and potentially also for deciding which parts of a cancer need to be treated."

Professor Joakim Lundeberg from KTH Royal Institute of Technology said: "Mapping thousands of tissue regions in a single experiment is an unprecedented approach to decipher the heterogeneity of tumors and their microenvironment. This high-resolution view influences the way we view complex ecosystems such as the ability to detect early events is special for the future exciting."

In addition, the researchers analyzed more than 150,000 regions in three prostate, two breast, skin, lymph node and brain tissues and developed an algorithm to track groups of cells with similar genetic changes - clones - to their precise location. This approach allowed them to zoom directly from visible tissue, through microscopic multicellular structures, and directly into the genes themselves, while keeping an eye on the overall landscape of the tissue.

Source:

University of Oxford

Reference:

Erickson, A. et al. (2022) Spatially resolved clonal copy number changes in benign and malignant tissues. Nature. doi.org/10.1038/s41586-022-05023-2.

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