The Power of Human Cancer Genetics as Revealed by Low-Grade Gliomas

Annu Rev Genet. 2019 Dec 3;53:483-503. doi: 10.1146/annurev-genet-120417-031642.

Abstract

The human brain contains a vast number of cells and shows extraordinary cellular diversity to facilitate the many cognitive and automatic commands governing our bodily functions. This complexity arises partly from large-scale structural variations in the genome, evolutionary processes to increase brain size, function, and cognition. Not surprisingly given recent technical advances, low-grade gliomas (LGGs), which arise from the glia (the most abundant cell type in the brain), have undergone a recent revolution in their classification and therapy, especially in the pediatric setting. Next-generation sequencing has uncovered previously unappreciated diverse LGG entities, unraveling genetic subgroups and multiple molecular alterations and altered pathways, including many amenable to therapeutic targeting. In this article we review these novel entities, in which oncogenic processes show striking age-related neuroanatomical specificity (highlighting their close interplay with development); the opportunities they provide for targeted therapies, some of which are already practiced at the bedside; and the challenges of implementing molecular pathology in the clinic.

Keywords: BRAF; DNA methylation; IDH; development; low-grade gliomas; next-generation sequencing; pediatric.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Age Factors
  • Brain / growth & development*
  • Brain / pathology
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Child
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Molecular Diagnostic Techniques
  • Mutation
  • Neurodevelopmental Disorders / genetics
  • Neurodevelopmental Disorders / pathology
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • raf Kinases / genetics

Substances

  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase 2, human
  • IDH1 protein, human
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • raf Kinases