title: Aurora kinase B is a potential therapeutic target in pediatric diffuse intrinsic pontine glioma.
abstract: Pediatric high-grade astrocytomas (HGAs) account for 15-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons--diffuse intrinsic pontine gliomas (DIPG). Assumptions that pediatric HGAs are biologically similar to adult HGAs have recently been challenged, and the development of effective therapeutic modalities for DIPG and supratentorial HGA hinges on a better understanding of their biological properties. Here, 20 pediatric HGAs (9 DIPGs and 11 supratentorial HGAs) were subject to gene expression profiling following approval by the research ethics board at our institution. Many of these tumors showed expression signatures composed of genes that promote G1/S and G2/M cell cycle progression. In particular, Aurora kinase B (AURKB) was consistently and highly overexpressed in 6/9 DIPGs and 8/11 HGAs. Array data were validated using quantitative real-time PCR and immunohistochemistry, as well as cross-validation of our data set with previously published series. Inhibition of Aurora B activity in DIPG and in pediatric HGA cell lines resulted in growth arrest accompanied by morphological changes, cell cycle aberrations, nuclear fractionation and polyploidy as well as a reduction in colony formation. Our data highlight Aurora B as a potential therapeutic target in DIPG.
authors.affiliation: Division of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Pawel
authors.initials: P
authors.lastname: Buczkowicz
authors.forename: Maryam
authors.initials: M
authors.lastname: Zarghooni
authors.forename: Ute
authors.initials: U
authors.lastname: Bartels
authors.forename: Andrew
authors.initials: A
authors.lastname: Morrison
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Misuraca
authors.forename: Tiffany
authors.initials: T
authors.lastname: Chan
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
authors.forename: Annie
authors.initials: A
authors.lastname: Huang
authors.forename: Oren
authors.initials: O
authors.lastname: Becher
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D015153:Blotting, Western; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002648:Child; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases