title: Oligonucleotide array-based comparative genomic hybridization (aCGH) of 90 neuroblastomas reveals aberration patterns closely associated with relapse pattern and outcome.
abstract: The study of genomic alterations in neuroblastoma is of particular importance since several cytogenetic markers proved to be closely associated with the clinical phenotype. To disclose patterns of gains and losses, we performed high-resolution oligonucleotide array-based comparative genomic hybridization (aCGH). A total cohort of 90 patients was classified into 6 subsets according to tumor stage and outcome: Stages 1-3+ (with event), Stage 1-3- (no event), Stage 4+/-, and Stage 4S+/-. The aberration patterns in Stages 1-3- and 4S- tumors differed from all other groups as they were predominantly characterized by losses (3, 4, 14, X) and gains (7, 17) of whole chromosomes. However, 59/65 (91%) tumors of Stages 1-3+ or Stage 4 revealed numerous structural copy number alterations (sCNA). While deletions in chromosomes 1, 3, and 11 discriminated outcome in Stage 4, there were no specific sCNA that distinguished tumor stage within the subgroup of unfavorable tumors. sCNA in 1p, 3p, 11q, 17q, or MYCN amplification (MNA) was seen among 22/24 patients who died, 10/12 with metastatic relapses, and 5/9 with local recurrences. Detailed breakpoint analyses on chromosomes 1, 3, 11, and 17 disclosed preferred breaking areas, although breakpoints were not identical. Amplifications were found in 18 patients and involved 2p24 (MYCN) and other segments of chromosome 2, as well as regions on chromosome arms 6q, 12q, and 17q. One single feature in 21q21.1 (BU678720, without known function yet) attracted particular attention since five patients showed a homozygous loss of this sequence.
authors.affiliation: Children's Hospital, Department of Paediatric Oncology and Haematology, University of Cologne, Köln, Germany. ruediger.spitz@uk-koeln.de
authors.forename: Ruediger
authors.initials: R
authors.lastname: Spitz
authors.forename: Andre
authors.initials: A
authors.lastname: Oberthuer
authors.forename: Marc
authors.initials: M
authors.lastname: Zapatka
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.forename: Karen
authors.initials: K
authors.lastname: Ernestus
authors.forename: Joern
authors.initials: J
authors.lastname: Oestreich
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Simon
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
mesh_terms: D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002874:Chromosome Mapping; D015331:Cohort Studies; D005784:Gene Amplification; D015894:Genome, Human; D006801:Humans; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012008:Recurrence