Cellular Signs of Kidney Tumors Found-ScienceDaily

Research published today (June 23) Nature CommunicationsAnalyzed existing datasets using computational techniques to identify the “cell signals” that are emitted when various cancers appear. This method is a promising tool for diagnosing rare cancer patients. In this study, a patient’s latent renal cell carcinoma was identified as a Wilms-like tumor by examining its cellular signals.

All cancers come from normal cells that have begun to grow out of control. By comparing the gene expression patterns of cancer and normal cells, it is possible to understand the origin and behavioral aspects of each tumor. This type of analysis has been made possible by the advent of single-cell mRNA sequencing, a high-resolution technique that can identify different cell types present in tissues according to genes expressed by individual cells.

Previous studies have used these techniques to compare normal and lesioned tissue in some of the most common kidney cancers, but it is not possible to perform a single-cell sequence in hundreds of tumors.

In this study, researchers at the Welcome Sanger Institute and their collaborators used computational techniques to mine Human Cell Atlas (HCA) reference data * and a database of tumor gene expression. To investigate the origin of these cancers, they evaluated mRNA signals in 1,300 childhood and adult kidney tumors across seven different tumor types **.

The results confirmed that these childhood cancers are of developmental origin and occur after an error on the path to maturation of a particular developmental cell type. In contrast, adult kidney cancer emerges from a mature cell type and most often does not revert to the developmental pattern of gene expression.

It has also been found that each cancer type exhibits a unique “cellular signal” or pattern of gene expression that can be used to classify them in the future.

Dr. Matthew Young, the first author of the Wellcome Trust Sanger Institute study, said: Various types of tumors can be seen. Our analysis also refutes the theory that adult tumors return to their developmental state unless they are a very deadly subtype of adult kidney cancer. “

This study sheds light on the behavior and origin of several kidney tumor subtypes whose rarity would have made it difficult to investigate otherwise. These were congenital mesoblastic nephoma, clear cell sarcoma of the kidney, malignant rhabdoid tumor of the kidney, and pigmented renal cell carcinoma.

The method pioneered in this study also helped clinicians classify tumors in one patient who could not be completely diagnosed.

Dr. Karin Straathof, senior author of the Great Ormond Street Hospital study, said: “The usual methods may not be able to completely diagnose childhood kidney cancer and may affect the ability to adopt the best treatment. The samples used in this study are these undiagnosed tumors. It was from a child with one of them, but by analyzing the genes expressed by the tumor cells, it could be recognized as a Wilms tumor. We hope that this approach can be used in such cases. Future case. “

In a recent study, researchers used mRNA single-cell sequencing in a small number of tumors to identify the origin of individual childhood cancers, such as neuroblastoma. Here, we use computational analysis of existing data to identify the origin of a larger group of childhood cancers.

Dr. Sambehati, senior author of the Wellcome Trust Sanger Institute’s research, said: “This computational approach using existing datasets not only validates previous results on the origin of childhood kidney cancer, but also makes this study more tumors and rare types of cancer. The success of this approach is in humans. I believe it could serve as a blueprint for investigating the behavior and origin of the full range of cancer. “

Note:

* Single-cell RNA sequencing (scRNAseq), which is used to assess which genes are active in individual cells, can be used in millions of cells at a time and produces vast amounts of data. .. The Human Cell Atlas project uses these techniques to identify and characterize all cell types present in an organism or population.

** The bulk transcriptome is a collection of gene expression in both tumor and normal cells. The types of cancer analyzed in this study are:

• Congenital mesoblastic nephoma (CMN)
• Wilms tumor (also known as Wilms tumor)
• Clear cell sarcoma of the kidney (CCSK)
• Malignant rhabdoid tumor of the kidney (MRTK)
• Clear cell renal cell carcinoma (ccRCC)
• Papillary renal cell carcinoma (pRCC), subtypes 1 and 2
• Pigmented Renal Cell Carcinoma (ChRCC), subtype “Metabolically Divergent ChRCC”