Understanding which cells give rise to which areas of cancer can improve our understanding of how a tumor has grown and developed, including how it has changed genetically, over time. This has been made possible by a new technique called spatial transcriptomics, which allows scientists to see what genetic changes are taking place without tearing apart the tissue they’re looking at. This adds a new dimension that researchers have now used to reveal which cells have mutated and where within an organ’s ecosystem.
Current techniques for studying the genetics of cells within tumors involve taking a sample from the cancerous area and analyzing the DNA of those cells. The problem is that many cancers, such as prostate cancer, are three-dimensional, meaning that any sample would only give 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 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 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.
Alastair Lamb, from Oxford’s Nuffield Department of Surgical Sciences, who co-led the study, said: “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.. One thing we’re pretty sure about 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 discovered that many of the copy number events that we previously thought were specifically linked to cancer are already present in benign tissue . This has huge implications for diagnosis and also potentially for deciding which parts of a cancer to treat.”
Professor Joakim Lundeberg of the KTH Royal Institute of Technology said: “Mapping thousands of tissue regions in a single experiment is an unprecedented approach to unraveling the heterogeneity of tumors and their microenvironment. This high-resolution view affects the way we approach complex ecosystems such as cancer. The ability to identify early events is particularly exciting going forward.”
In addition, the researchers analyzed 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 down groups of cells with similar genetic changes – clones- to their precise location. This approach allowed them to approach directly from visible tissue through microscopic multicellular structures and directly to the genes themselves, while maintaining the overall landscape of the tissue.
ENDS
The full paper, “Spatially resolved clonal copy number alterations in benign and malignant tissues,” is published in Nature.
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Notes to editors
The Nuffield Department of Surgical Sciences
The Nuffield Department of Surgical Sciences (NDS) at the University of Oxford is home to a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and trainee scientists. We train in the main surgical specialties, such as gastrointestinal, transplant, vascular, pediatric, plastic, ear, nose and throat (ENT), neurosurgery and urology. The research environment at 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, along with groups in cardiovascular and functional neurosurgery, high intensity focused ultrasound and urological oncology. In recent years, the department has expanded into areas of basic cancer research, pathology, bioinformatics and artificial intelligence. NDS is also home to multiple biobanks, a clinical trials center and a group of research nurses who support the research we do in the department. There are more than 200 employees in the department who work together to lead discovery, innovation and education in surgical science. www.nds.ox.ac.uk
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Research method
Experimental study
Research topic
Cells
Title of the article
Spatially resolved clonal copy number alterations in benign and malignant tissues
Publication date of the article
August 10, 2022