Ivy Glioblastoma Atlas

Atlas and the associated database to serve as a useful platform for developing and testing new hypotheses related to the pathogenesis, diagnosis, and treatment of glioblastoma

On 11 May 2018, the researchers from the Ivy Glioblastoma Atlas led by Ralph B. Puchalski of the Allen Institute for Brain Science, Seattle, WA, US published in Science an anatomically based transcriptional findings of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumour. The atlas and its clinical and genomic database are freely accessible online data resources. 

The authors wrote in study background that two large-scale efforts aimed at characterising the genomic alterations in human glioblastoma are The Cancer Genome Atlas (TCGA), which is a catalogue of multi-omics data, including genomics, transcriptomics, DNA methylomics, proteomics, etc., and Repository for Molecular Brain Neoplasia Data (REMBRANDT), which also includes multiple data domains. These efforts helped to clarify the role of genomic alterations in the pathogenesis of glioblastoma but were not designed to address intratumour heterogeneity. 

Subsequent studies addressed heterogeneity spatially within bulk tumour or at the single-cell level. However, a systematic understanding of the tumour’s molecular heterogeneity as it relates to anatomical heterogeneity was still lacking. By “anatomical heterogeneity,” the authors meant on the variable combination of the classical histological features of glioblastoma, such as tumour infiltration, endothelial cell proliferation, and necrosis. 

The Ivy Glioblastoma Atlas Project is a foundational resource for exploring the anatomic and genetic basis of glioblastoma at the cellular and molecular levels. The atlas, a collaborative effort between bioinformaticians and pathologists, maps molecular features of glioblastomas, such as transcriptional signatures, to histologically defined anatomical regions of the tumours. 

The Ivy Glioblastoma Atlas Project includes the following data sets: Image data at cellular resolution of in situ hybridization (ISH) tissue sections and adjacent haematoxylin and eosin (H&E)-stained sections annotated for anatomic structures; RNA sequencing data for anatomic structures identified in the Anatomic Structures ISH Survey and putative cancer stem cell clusters isolated by laser microdissection; specimen metadata: de-identified clinical data for each patient and tumour. Ivy GAP Clinical and Genomic Database is a partner database with additional clinical, genomic, and transcriptome data for each donor and tumour. 

The Ivy Glioblastoma Atlas represents a comprehensive molecular pathology map of glioblastoma with assigned key genomic alterations and gene expression profiles to the tumour’s anatomic features. The atlas will facilitate accurate deconvolution of anatomic features in new samples of glioblastoma, providing unique information for the comprehensive diagnostic characterisation of the tumour’s heterogeneity. The authors noted that investigators are already leveraging this resource. 

The Ivy Glioblastoma Atlas Project is a collaborative partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science, and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment. This project was supported by the Ben and Catherine Ivy Foundation (Principal Investigators: Ralph Puchalski, PhD, Allen Institute for Brain Science and Greg Foltz, MD, Swedish Neuroscience Institute). The authors wrote in the paper that this project is dedicated to Greg Foltz, a dedicated and talented neurosurgeon as well as a visionary in glioblastoma research, who passed away during the course of the study. 

Reference 

Puchalski RB, Shah N, Miller J, et al. An anatomic transcriptional atlas of human glioblastoma. Science 2018; 360(6389):660-663. DOI: 10.1126/science.aaf2666