Genetic Architectures and Cell-of-Origin in Glioblastoma.

Hyun Jung Kim,Jeong Ho Lee,Jung Won Park

doi:10.3389/fonc.2020.615400

Hyun Jung Kim, Jeong Ho Lee + Show 1 more

Open Access

https://doi.org/10.3389/fonc.2020.615400

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Abstract

An aggressive primary brain cancer, glioblastoma (GBM) is the most common cancer of the central nervous system in adults. However, an inability to identify its cell-of-origin has been a fundamental issue hindering further understanding of the nature and pathogenesis of GBM, as well as the development of novel therapeutic targets. Researchers have hypothesized that GBM arises from an accumulation of somatic mutations in neural stem cells (NSCs) and glial precursor cells that confer selective growth advantages, resulting in uncontrolled proliferation. In this review, we outline genomic perspectives on IDH-wildtype and IDH-mutant GBMs pathogenesis and the cell-of-origin harboring GBM driver mutations proposed by various GBM animal models. Additionally, we discuss the distinct neurodevelopmental programs observed in either IDH-wildtype or IDH-mutant GBMs. Further research into the cellular origin and lineage hierarchy of GBM will help with understanding the evolution of GBMs and with developing effective targets for treating GBM cancer cells.

Highlights

Glioblastoma (GBM) is a common, but aggressive, primary brain cancer of the central nervous system in adults and is associated with poor prognosis due to its invasiveness and resistance to therapy
We mainly focus on the cell-of-origin in GBM and discuss the recent genomic analyses of GBM and genetically engineered mouse models (GEMMs) investigating tumorigenesis of GBM
We summarize in the following paragraphs key somatic mutations, known as driver mutations, frequently occurring in Isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant GBM, respectively (Figure 1)

Summary

INTRODUCTION

Glioblastoma (GBM) is a common, but aggressive, primary brain cancer of the central nervous system in adults and is associated with poor prognosis due to its invasiveness and resistance to therapy. Identifying the cellular origin of GBM would help with further understanding of tumor initiation/propagation and effective targets of use in treating GBM cancer cells. Genetics and Cell-of-Origin in Glioblastoma occur and accumulate to initiate tumor formation, while cancer stem cells (CSCs) refers to a subset of proliferating cancer cells that sustain tumor growth [8]. The CSCs in GBM have been wellreviewed in many other papers [9,10,11]. In this mini review, we mainly focus on the cell-of-origin in GBM and discuss the recent genomic analyses of GBM and genetically engineered mouse models (GEMMs) investigating tumorigenesis of GBM

GENETIC ALTERATIONS IN GLIOBLASTOMA

DISSECTING CELLULAR HIERARCHY IN GLIOBLASTOMA

Findings

DISCUSSION