Knowing which cells give rise to certain types of cancer can help us better understand how a tumor has grown and evolved over time, including how its genetic makeup has changed.

This has been made feasible by a novel method called spatial transcriptomics, which enables researchers to examine genetic alterations without dissecting the tissue under study.

This adds a new dimension that researchers may now utilize to determine which cells have mutated and where within an organ’s ecology.

Current methods for researching the genetics of cells within tumors include collecting a sample from the malignant area and analyzing the DNA of those cells.

The issue is that many tumors, such as prostate cancer, are three-dimensional, meaning that any single sample would only provide a slice of the tumor.

A cross-sectional map of an entire prostate, including regions of healthy and malignant cells, was made using spatial transcriptomics in a recent work that was supported by Cancer Research UK and published in Nature.

They were astonished to find regions of seemingly healthy tissue that already contained many of the genetic traits of malignancy after grouping cells based on comparable genetic identities.

This discovery was remarkable due to both the genetic variety within the tissue and the vast number of cells that would normally be considered healthy but possessed mutations typically associated with malignant cells.

“Prostate tissue is three-dimensional,” adds Alastair Lamb of Oxford’s Nuffield Department of Surgical Sciences, who jointly led the study, “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,” they “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.”

Mapping thousands of tissue locations in a single experiment is an unparalleled way to deconvolute the heterogeneity of cancers and their microenvironment, according to Professor Joakim Lundeberg of KTH Royal Institute of Technology.

This high-resolution perspective affects how we approach complicated ecosystems like cancer. Going forward, the potential for early event detection is especially exciting.

Additionally, the researchers built an algorithm to track collections of cells with similar genetic changes—clones—in their specific position by analyzing more than 150,000 locations in three prostates, two breast malignancies, some skin, a lymph node, and some brain tissue.

They were able to maintain sight of the general tissue landscape while zooming in from the visible tissue via minute multicellular structures and into the genes themselves.

Source: 10.1038/s41586-022-05023-2

Image Credit: Getty

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