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Molecular characteristics of diffuse lower grade gliomas: what neurosurgeons need to know

  • Review Article - Tumor - Glioma
  • Published:
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Abstract

The importance of genomic information in intrinsic brain tumors is highlighted in the World Health Organization (WHO) 2016 classification of gliomas, which now incorporates both phenotype and genotype data to assign a diagnosis. By using genetic markers to both categorize tumors and advise patients on prognosis, this classification system has minimized the risk of tissue sampling error, improved diagnostic accuracy, and reduced inter-rater variability. In the neurosurgical community, it is critical to understand the role genetics plays in tumor biology, what certain mutations mean for the patient’s prognosis and adjuvant treatment, and how to interpret the results of sequencing data that are generated following tumor resection. In this review, we examine the critical role of genetics for diagnosis and prognosis and highlight the importance of tumor genetics for neurosurgeons caring for patients with diffuse lower grade gliomas.

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Abbreviations

LGG:

Low-grade glioma

GBM:

Glioblastoma

WHO:

World Health Organization

IDH:

Isocitrate dehydrogenase

GWAS:

Genome wide association study

IHC:

Immunohistochemistry

2-HG:

2-Hydroxyglutarate

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Authors and Affiliations

  1. Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA

    Jacob S. Young, Andrew J. Gogos, Ramin A. Morshed, Shawn L. Hervey-Jumper & Mitchel S. Berger

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  1. Jacob S. Young
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This valuable review deals with the current molecular and histological classification of low-grade gliomas and addresses the therapeutic and prognostic implications of such recent acquisitions. References are appropriate and the timeline highlighted in Table 1, of help in summarizing the pivotal discoveries of this field. Since Bailey and Cushing’s proposal in 1926, human gliomas have been classified according to their histological features, lineage of differentiation, and putative embryological origin. In the course of the twentieth century, Bailey and Cushing’s model inspired huge achievements on glioma biology, leading to a progressive refinement of these tumors’ classification.

In recent years, the understanding of the molecular events driving gliomagenesis set the bases for novel integrated definitions of each tumor entity. This approach is endorsed by the current WHO classification of central nervous system tumors, which (for the first time in the history of glioma classification) identifies both pathological and molecular criteria for their diagnosis. Yet, for sure, this is not the end of a century long medical adventure.

Since the publication of the 2016 WHO classification, many steps forward have been taken, which will likely change the landscape of glioma diagnosis, therapy, and prognostic stratification. These novel acquisitions include (i) tumor epigenetic and methylation profiles, (ii) single cell resolution of molecular and metabolic features, (iii) the characterization of intra-tumor clonal heterogeneity, and (iv) an in-depth definition of the tumor microenvironment. These studies highlight a much more complex scenario than previously thought and pose challenging questions to the current neuro-oncology practice.

Only a tight collaboration among health professionals will succeed in the management of these complex diseases.

Domenico d’Avella and Marco Pizzi Padova, Italy

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This article is part of the Topical Collection on Tumor - Glioma

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Young, J.S., Gogos, A.J., Morshed, R.A. et al. Molecular characteristics of diffuse lower grade gliomas: what neurosurgeons need to know. Acta Neurochir 162, 1929–1939 (2020). https://doi.org/10.1007/s00701-020-04426-2

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