59. Inferring copy number events in Glioblastoma using spatial gene expression data

Aly Abdelkareem

Samuel Brown

Samuel is a MSc. student in the Morrissy Lab at the University of Calgary. He obtained his Bachelor of Science in Kinesiology (honours) from Queen’s University in Kingston, Ontario. Samuel joined the lab in 2018 as a summer student and has returned every subsequent summer to learn cancer analysis methods and work on several projects related to tumour heterogeneity. With career plans to be a clinician-scientist Samuel is excited to delve deeper into cancer bioinformatics analyses during his graduate research on sarcomas. His thesis project is focused on using spatial transcriptomics data to understand tumour and immune cell adaptations to radiotherapy in soft tissue sarcomas. These skills are further utilized in his work on GBM using spatial transcriptomics and bioinformatic methods. Samuel looks forward to broadening his understanding of oncology at the Cancer Genomics Consortium!


Samuel Brown, Aly Abdelkareem, Aaron Gillmor, Heewon Seo, Kata Osz, Jennifer A. Chan, Sorana Morrissy

University of Calgary, Calgary, Alberta, CA

Background: Glioblastoma (GBM) is the most common malignant brain tumour in adults, with inevitable treatment resistance and poor outcomes. Genomic instability of GBM gives rise to large-scale chromosomal copy number variants (CNVs) that drive resistance. Genetically distinct clones in GBM are conventionally investigated using whole-genome sequencing (WGS), but recent bioinformatic approaches can infer CNVs using transcriptomics data only.

Purpose: To investigate whether patient-derived xenograft (PDX) mouse models of GBM exhibit clonal diversity as a function of space (across tumour regions) and time (early to late time points).

Methods: PDX data from 3 cell lines representing the tumour core, vascular regions, and infiltrating edge of one GBM patient’s tumour were profiled at early and late time points in disease progression, using the 10X Genomics Visium platform for spatial transcriptomics. The computational tool inferCNV was used to identify CNVs.

Results: Successfully identified large-scale CNVs were concordant with events detected in matched WGS data. Additionally, we identified a minor subclone not detectable by WGS that expands in multiple PDX mice indicating it is pre-existing in the patient-derived cell lines. Further analysis revealed localization of this subclone to the tumour core region suggesting a microenvironment-specific adaptation.

Conclusions: We show that spatial gene expression data can be leveraged to infer CNVs in PDX models of GBM that correspond to known events from bulk WGS data. Subclones present below the limit of WGS detection can also be inferred. Charting the spatially resolved position of these clones in vivo supports the use of PDX models in GBM.