title: Pathology, Molecular Genetics, and Epigenetics of Diffuse Intrinsic Pontine Glioma.
abstract: Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric brain cancer with no effective therapy. Histological similarity of DIPG to supratentorial high-grade astrocytomas of adults has led to assumptions that these entities possess similar underlying molecular properties and therefore similar therapeutic responses to standard therapies. The failure of all clinical trials in the last 30 years to improve DIPG patient outcome has suggested otherwise. Recent studies employing next-generation sequencing and microarray technologies have provided a breadth of evidence highlighting the unique molecular genetics and epigenetics of this cancer, distinguishing it from both adult and pediatric cerebral high-grade astrocytomas. This review describes the most common molecular genetic and epigenetic signatures of DIPG in the context of molecular subgroups and histopathological diagnosis, including this tumor entity's unique mutational landscape, copy number alterations, and structural variants, as well as epigenetic changes on the global DNA and histone levels. The increased knowledge of DIPG biology and histopathology has opened doors to new diagnostic and therapeutic avenues.
authors.affiliation: Division of Pathology, The Hospital for Sick Children , Toronto, ON , Canada ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children , Toronto, ON , Canada.
authors.forename: Pawel
authors.initials: P
authors.lastname: Buczkowicz
authors.affiliation: Division of Pathology, The Hospital for Sick Children , Toronto, ON , Canada ; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children , Toronto, ON , Canada ; Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto , Toronto, ON , Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
keywords: ACVR1; DIPG; H3F3A; K27M; glioblastoma; glioma; histone; pediatric