title: Detrended fluctuation analysis of genome-wide copy number profiles of glioblastomas using array-based comparative genomic hybridization.
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 (alpha2) 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.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, Saga University, Saga 849-850, Japan. nakahara@post.saga-med.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakahara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Mineta
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Oishi
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tabuchi
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016019:Survival Analysis