High-resolution, dual-platform aCGH analysis reveals frequent HIPK2 amplification and increased expression in pilocytic astrocytomas.
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.
Deshmukh
H
H
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Yeh
T H
TH
Yu
J
J
Sharma
M K
MK
Perry
A
A
Leonard
J R
JR
Watson
M A
MA
Gutmann
D H
DH
Nagarajan
R
R
D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D004252:DNA Mutational Analysis / Q000295:instrumentation / Q000379:methods; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling / Q000295:instrumentation / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D002352:Carrier Proteins; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases