Single Nuclear RNA-seq and Spatial Transcriptomic Analysis of Anaplastic and Favorable Histology Wilms Tumor
Lay Summary: Wilms tumor is the most common pediatric kidney cancer. The best predictor of clinical outcome for Wilms tumor patients is how their tumor looks under the microscope (histology). The majority of Wilms tumor patients have favorable histology tumors that respond to surgery, chemotherapy, and radiation. These tumors are usually called triphasic tumors because they contain three main cell types--epithelial cells, blastemal cells, and stromal cells. A favorable histology Wilms tumor may transition into an unfavorable histology tumor by developing anaplasia (strikingly abnormal cellular divisions seen under the microscope). Unfavorable histology tumors (diffuse anaplasia) account for 5% of Wilms tumor cases but are resistant to treatment and are responsible for 50% of deaths from this disease. Usually, the resistant/anaplastic component of the tumor makes up only a fraction of the total number of cells in the cancer. A critical barrier to understanding therapeutic resistance in this disease is that studies performed to sequence the resistant component is diluted by the other components of the tumor. Therefore, the current proposal aims to use two technologies (single-nuclear-RNA sequencing and spatial transcriptomics) to isolate the gene expression patterns of individual cell types in Wilms tumor and to focus on the anaplastic/resistant cells.
Lay Summary Project Goal: The goal of this project is to use single-nuclear-RNA sequencing and spatial transcriptomics to determine the gene expression signature of the three cell types in Wilms tumor (epithelia, blastema, stroma) and the therapy-resistant cells (anaplastic cells) in unfavorable histology Wilms tumor. Single nuclear RNA sequencing is one way of sequencing individual cells in a tumor. Spatial transcriptomics allows the research team to visually identify where genes are being expressed in each tissue sample. These techniques will allow us to determine the expression signatures of the various cell types and resistant cells in Wilms tumor with greater confidence. This study is likely to increase our understanding of resistant cells in Wilms tumor. It will be an important foundation for thinking about ways to overcome this resistance and improve treatments for these patients.