title: Chromosome 17/17q gain and unaltered profiles in high resolution array-CGH are prognostically informative in neuroblastoma.
abstract: The prognostic relevance of chromosome 17 gain in neuroblastoma is still discussed. This investigation specifies the frequency, type, size, and transcriptional relevance in a large patient cohort. Primary tumor material of 202 patients was analyzed using high-resolution oligonucleotide array-based comparative genomic hybridization (aCGH) and correlated with clinical and survival data. A subset (n = 145) was correlated for differentially expressed genes (DEG) by microarray analysis. Chromosome 17 aCGH analysis showed numerical gain in 94/202 patients (47%), partial gain in 93/202 patients (46%), and no gain in 15/202 patients (7%). The frequency of partial gain was higher in stage 4 neuroblastoma (stage 1 15%; stage 2 12%; stage 3 16%; stage 4S 7%; and stage 4 50%). Overall survival (OS) was superior in patients with numerical gain compared with patients with partial gain or no gain (5-y-OS: 0.95 ± 0.02 vs. 0.63 ± 0.05 vs. 0.60 ± 0.13; P < 0.001). Gene expression analysis demonstrated 95/130 DEGs between tumors with numerical or partial chromosome/no gain. Only one DEG (CCKBR) was detected comparing tumors with partial gain and those with no gain. In patients with partial gain, the distribution of breakpoints did not correlate with stage and 11q status, but with MYCN amplification and 1p status. The "best" breakpoints in cases with partial 17q gain were at 42.5 Mb for event-free and 26.6 Mb for OS. Numerical gain of chromosome 17 is associated with a better prognosis than partial and no gain. The group of tumors with partial gain was similar to the group without gain with respect to stage distribution, outcome, and gene expression profile.
authors.affiliation: Department of Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, Cologne, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Theissen
authors.forename: Andre
authors.initials: A
authors.lastname: Oberthuer
authors.forename: Anja
authors.initials: A
authors.lastname: Hombach
authors.forename: Ruth
authors.initials: R
authors.lastname: Volland
authors.forename: Falk
authors.initials: F
authors.lastname: Hertwig
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.forename: Ruediger
authors.initials: R
authors.lastname: Spitz
authors.forename: Marc
authors.initials: M
authors.lastname: Zapatka
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Monika
authors.initials: M
authors.lastname: Ortmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Simon
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
mesh_terms: D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D059467:Transcriptome