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Molecular Genetics |
Department of Neurosurgery, Faculty of Medicine, Saga University, Saga 849-8501 (Y.N., T.S., H.O., T.M., T.O., K.T.); Department of Pathology, Yamaguchi University School of Medicine, Ube 755-8505 (K.S.); Japan
3 Address correspondence to Yukiko Nakahara, Department of Neurosurgery, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan (nakahara{at}post.saga-med.ac.jp).
Abstract
We examined whole genomic aberrations of biopsied samples from 19
independent glioblastomas by array-based comparative genomic hybridization
analysis. The highest frequencies of copy number gains were observed on
RFC2 (73.3%), EGFR (63.2%), and FGR, ELN, CDKN1C, FES,
TOP2A, and ARSA (57.9% each). The highest frequencies of copy
number losses were detected on TBR1 (52.6%), BMI1 (52.6%),
EGR2 (47.4%), DMBT1 (47.4%), MTAP (42.1%), and
FGFR2 (42.1%). The copy number gains of CDKN1C and
INS and the copy number losses of TBR1 were significantly
correlated with longer survival of patients. High-level amplifications were
identified on EGFR, SAS/CDK4, PDGFRA, MDM2, and ARSA. These
genes are assumed to be involved in tumorigenesis or progression of
glioblastomas. The first attempts to apply detrended fluctuation analysis to
copy number profiles by considering the reading direction as the time axis
demonstrated that higher long-term fractal scaling exponents (
2)
correlated well with longer survival of glioblastoma patients. The present
study indicates that array-based comparative genomic hybridization analysis
has great potential for assessment of copy number changes and altered
chromosomal regions of brain tumors. Furthermore, we show that nonlinear
analysis methods of whole genome copy number profiles may provide prognostic
information about glioblastoma patients.
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