Everyone has some kind of experience with cancer throughout their lives. Whether they undergo the battle themselves or know a family member or friend fighting through it, most people know how difficult of an experience can be to get through. The thought of finding the cure to cancer feels like an idea that parallels world peace.
Cancer is a genetic disease where cells grow uncontrollably and spread throughout the body (What is Cancer? 2021). It can spread to multiple places in the body after infiltrating into the blood, which can be incredibly dangerous and harmful to the human body and, in many cases, can lead to death. These mutations can be precursory changes to the genes that were passed down through parents or can be caused by environmental factors, such as radiation. The resulting mutations remove the signals from the cell that tell it to stop growing, causing the cell to duplicate uncontrollably, leading to a tumor, better known as cancer.
Cancer research is an important and prevalent topic in society and new revelations are built upon it almost every year. Over the past few years, the study of the human genome has also been a popular, up-and-coming topic of research and it is constantly being developed. A method that started growing in the 1960s combines the fascinating field of genomics and the study of cancer but in a more in-depth and less invasive way.
This fusion method is called spatial transcriptomics and it uses genome mapping to study organs in the body affected by cancer. So far, this method has mainly been used to look at prostate cancer. It gives researchers and doctors a way to see the organ as a whole and compare the healthy cells directly to cancerous cells, without having to use an invasive method, like taking a biopsy. They can use this technique to see the origins of how the cells become cancerous and the specific mutations that could have caused them to result in the overgrowth. They use a technique specifically called genome-derived analysis (siCNVs), which is an analysis procedure that shows the direct expression of the genes throughout a tissue sample. The data is then studied to see if there are any discrepancies that might indicate the initial point of mutation.
An article about the development of this method was published in 2021 by A. Erickson, M. He, et al called “Spatially resolved clonal copy number alterations in benign and malignant tissue.” They discuss this method of spatial transcriptomics and its implications in the advancement in cancer research. This technique is specifically used to find the less common genetic events that take place in cells that are not a direct result of a genetic mutation. Researchers use in situ* mRNA profiles to infer the copy number variations (CNVs), the trait that refers to the amount of copies a particular gene expresses in an individual genome (Erickson et al 360). Each of these profiles consists of barcoded spots that are then used to create a DNA-based phylogenetic tree of the RNA samples from the organ. The phylogenetic tree can be used to track the clonal relationships between the multifocal tumors (Erickson et al 360). They generate these barcodes by using sequencing libraries and amplifying the transcription that is created in vitro (Ståhl et al 2016). Then, in order to assess the organ thoroughly through this method, it is broken up into 5×5 mm^2 blocks. They specifically use a technique called siCNVs (genome-derived analysis copy number variations) to create a cross section of the organ that is being studied to check for multifocal malignancy, which is when tumors stem from multiple points in one organ. The researchers in this study also created a phylogenetic tree to track the clonal events happening in the cells and eventually be able to see where the mutations were specifically taking place.
All of the patients that were studied during the experiment had written and verbal information about the process and methods of the study, so ethics was not an issue. One possible limitation to this study could be the lack of variety of organs that were studied. In this study, they specifically looked at lymph node cancer, glioblastomas, and breast cancer (Erickson et al 368). Studying an even wider variety of organs affected with different types of cancer would give a better idea of how this method can be used to diagnose and treat cancer patients. Diversifying the subjects of study would improve the future implications of the work.
A limitation noted by the researchers is related to the fact that spatial transcriptomics is a single-cell method. For that reason, it is likely that the genome-derived analysis will not be able to capture single-nucleotide variant mutations or other copy number-neutral events (Erickson et al 362). This limitation could cause a discrepancy in the data. For example, there could be a tumor that could result from a mutation that was not detected by the genome-derived analysis method because it is unable to apprehend a mutation that stems from multiple places.
But why is spatial transcriptomics important for the future of cancer research? “With spatial transcriptomics, we can link the distribution of cells in the tumor microenvironment with genes that may regulate position or interaction with other cells,” says Tuilla Bruno, an immunologist from the University of Pittsburgh (NatureResearch). Until this method of spatial transcriptomics, the study of tumors has relied on looking at individual tissues of tumors. This traditional method is neither efficient nor does it give the complete picture of the tumor. RNA and DNA sequencing provides an unprejudiced view on the gene expressions throughout the genome (NatureResearch).
Spatial transcriptomics has proven to be a phenomenal method to study cancer. It can be used to directly look at mutations that cause the tumor to form and help doctors give better diagnosis and treatment options for patients. As time progresses, researchers and doctors will be able to use this method of spatial transcriptomics to study the origins of a variety of cancers, from brain to blood to lung. In the current time, spatial transcriptomics has brought us a huge step closer towards finding the cure to cancer.
*in the original place
Bibliography
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Erickson A, He M, Berglund E, Marklund M, Mirzazadeh R, Schultz N, Kvastad L, Andersson A, Bergenstråhle L, Bergenstråhle J, et al. 2022. Spatially resolved clonal copy number alterations in benign and malignant tissue. Nature. https://www.nature.com/articles/s41586-022-05023-2.
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What is Cancer? 2021. National Cancer Institute. https://www.cancer.gov/about-cancer/understanding/what-is-cancer.
Photo by Coneyl Jay from Medical News Today
By Aashvi Jain