Low-grade gliomas are the most prevalent brain cancer among children. While patients with this type of cancer respond well to surgery, the majority experience recurrence after initial resection, requiring additional rounds of treatment that are rarely guided by molecular information. Intra-tumoural clonal heterogeneity and tumour microenvironment are two main factors that together contribute to disease recurrence. Using single-cell sequencing technology, recent reports have shown the extent of heterogeneity in gliomas shedding light into complex.
For the past year, we have been studying the immune microenvironment of over 1100 samples of pediatric cancers at primary diagnosis using bulk RNAseq datasets from three sources including CBTN. We found high variability of immune infiltrates across cancers as well as specific immune cell types enriched within specific cancers including low-grade glioma.
The overall aim of this proposal is to delineate changes in malignant and non-malignant compartments of pediatric low-grade gliomas during the course of the disease using single-nuclei sequencing.
What are the goals of this project?
The goals of this project are to determine changes in tumour subclonal populations during course of tumour progression and to investigate contribution and evolution of tumour microenvironment in the low-grade glioma.
What is the impact of this project?
By studying cancer and non-cancerous cell types that populate brain tumours upon recurrence, we expect to nominate cell dependencies that may be disrupted therapeutically and clonal populations that may respond to synergistic combination therapies. Over time, we expect our primary/relapse paradigm to increase in impact as additional tumours are contributed to the Single-cell Pediatric Cancer Atlas and mapped to mechanisms we have uncovered in this first set of patients.
Why the CBTN request is important to this project?
The CBTN provides a large cohort of samples from children and young adults with brain tumours. There are several sets of serial frozen tissues from patients with low- grade gliomas with matching bulk whole genome and RNAseq data. Longitudinal clinical, treatment and genomic data are available from these samples making them a unique valuable sample set to address our specific aims.
The Children's Brain Tumor Network will be contributing to this project by providing low grade glioma samples.
Low-Grade astrocytomas are the most common cancer of the central nervous system in children. They represent a heterogeneous group of tumors that can be discovered anywhere within the brain or spinal cord. Although surgical resection may be curative, up to 20% of children still suffer from the eff
Immunogenomic Landscape of Pediatric Cancers
The goal of this study is to determine the overall layout of infiltrating immune repertoire in pediatric solid tumors. We will perform immune repertoire analysis and deconvolute immune components from RNA-seq data using transcript counts to infer the fraction of ~20 immune cell types infiltrating