1. ¹Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
2. ²Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
3. ³Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, USA
4. ⁴Department of Neurology, Chang Gung Memorial Hospital and University, Taipei, Taiwan

Correspondence: Dr DH Gutmann, Department of Neurology, Washington University School of Medicine, 660 S. Euclid Avenue, 306 Biotechnology Building, Campus Box 8111, St Louis, MO 63110, USA. E-mail: gutmannd@neuro.wustl.edu; Dr R Nagarajan, Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8118, St Louis, MO 63110, USA. E-mail: rakesh@wustl.edu

⁵These authors contributed equally to this work.

Received 11 December 2007; Revised 24 January 2008; Accepted 1 March 2008; Published online 14 April 2008.

Abstract

Pilocytic astrocytomas (PAs, WHO grade I) are the most common brain tumors in the pediatric and adolescent population, accounting for approximately one-fifth of central nervous system tumors. Because few consistent molecular alterations have been identified in PAs compared to higher grade gliomas, we performed array comparative genomic hybridization using two independent commercial array platforms. Although whole chromosomal gains and losses were not observed, a 1-Mb amplified region of 7q34 was detected in multiple patient samples using both array platforms. Copy-number gain was confirmed in an independent tumor sample set by quantitative PCR, and this amplification was correlated to both increased mRNA and protein expression of HIPK2, a homeobox-interacting protein kinase associated with malignancy, contained within this locus. Furthermore, overexpression of wild-type HIPK2, but not a kinase-inactive mutant, in a glioma cell line conferred a growth advantage in vitro. Collectively, these results illustrate the power and necessity of implementing high-resolution, multiple-platform genomic analyses to discover small and subtle, but functionally significant, genomic alterations associated with low-grade tumor formation and growth.