Genetic Hallmarks and Heterogeneity of Glioblastoma in the Single-Cell Omics Era

Abstract

Glioblastoma multiforme is the most common and aggressive malignant primary brain tumor. As implied by its name, the disease displays impressive intrinsic heterogeneity. Among other complications, inter- and intratumoral diversity hamper glioblastoma research and therapy, typically leaving patients with little hope for long-term survival. Extensive genetic analyses, including omics, characterize several recurrent mutations. However, confounding factors mask crucial aspects of the pathology to conventional bulk approaches. In recent years, single-cell omics have made their first appearance in cancer research, and the methodology is about to reach its full potential for glioblastoma too. Here, recent glioblastoma single-cell omics investigations are reviewed, and most promising routes toward less grim prognoses and more efficient therapeutics are discussed.

Keywords: glioblastoma; glioblastoma multiforme heterogeneity; omics; single cells.

Figure 1

Logical relationships between research in glioblastoma, omics, and techniques with single-cell resolution. An Euler diagram shows criteria setting the requirements for a study to be considered of primary interest for the review. GBM, glioblastoma multiforme; SC, single cell.

Figure 2

Single-cell omics push a shift in paradigm for glioblastoma study and treatment. Each of the four sketches on the left depicts a glioblastoma (GBM) site (pale borderless head area) with a representation of cell lineages found in it, circles representing cancer cells, squares symbolizing surrounding non-tumor cells (colors mark individual lineages, connecting lines indicate hypothetical phylogenetic relationships between GBM cells). “Research, diagnosis or therapy” tables report a simplification of typical outcomes for each of the three exemplified approaches to research, diagnosis, or treatment for GBM. Object colors indicate cell lines dictating results; their size correlates with the magnitude of the distinguishable signal they generate, and their shape indicates whether they can exquisitely associate a given signal to either tumor (circles) or surrounding (squares) cells. IDH-A, IDH-mutant astrocytoma; IDH-O, IDH-mutant oligodendroglioma; GSC, glioblastoma stem cell; SC, single cell; TCGARN, The Cancer Genome Atlas Research Network.