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

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

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Pediatric Glioma Research Group, Hopp Children's Cancer Center Heidelberg (KiTZ), 69120 Heidelberg, Germany.
German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts 02215, USA.
The Broad Institute of MIT and Harvard, Boston, Massachusetts 02142, USA.
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Departments of Pediatric and Human Genetics, McGill University and the Research Institute of the McGill University Health Center, Montreal, Quebec H4A 3J1, Canada; email:


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.


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

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