Open AccessA urora Kinase B Is a Potential Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma
Author(s) -
Buczkowicz Pawel,
Zarghooni Maryam,
Bartels Ute,
Morrison Andrew,
Misuraca Katherine L.,
Chan Tiffany,
Bouffet Eric,
Huang Annie,
Becher Oren,
Hawkins Cynthia
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2012.00633.x
Subject(s) - cancer research , pons , immunohistochemistry , glioma , medicine , cell cycle , pathology , cancer
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 A urora B as a potential therapeutic target in DIPG .