title: Combined 24-color karyotyping and comparative genomic hybridization analysis indicates predominant rearrangements of early replicating chromosome regions in neuroblastoma.
abstract: Neuroblastoma is characterized by several distinct genetic alterations including MYCN amplification, chromosome 1p deletion and gain of chromosome 17. Although these alterations are thought to play a crucial role in oncogenesis, to date little is known about their underlying mechanisms. In order to more precisely document these genetic alterations, we have performed a combined study of 27 neuroblastoma cell lines using 24-color karyotyping (24-CK) and comparative genomic hybridization (CGH). 24-CK detected balanced translocations in 13 cases with recurrent involvement of chromosome 8. More importantly, 144 nonreciprocal translocations were observed in the 27 cell lines, with chromosome 1 as the most frequent recipient and chromosome 17 the most frequent donor. Each cell line exhibited at least one unbalanced translocation involving 17q, with 14 cell lines demonstrating more than one such translocation. Other recurrent alterations were amplification of the 2p24 chromosome region, which encodes the MYCN oncogene, losses of 1p, 3p and 11q, and gains of 1q and 7. In most cases, CGH profiles were directly linked to the presence of unbalanced translocations with gain of the donor fragment and loss of the replaced region on the recipient chromosome. Strikingly, over 60% of the chromosome breakpoints mapped to early replicating chromosome bands, which represent around 13% of the genome. Altogether these data suggest that neuroblastoma is characterized by rearrangements that predominantly involve chromosome fragments replicating early in the S-phase.
authors.affiliation: INSERM Unité 509, Laboratoire de Pathologie Moléculaire des Cancers, Institut Curie, 26 rue d'Ulm, 75248 Cedex 05, Paris, France.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schleiermacher
authors.forename: Isabelle
authors.initials: I
authors.lastname: Janoueix-Lerosey
authors.forename: Valérie
authors.initials: V
authors.lastname: Combaret
authors.forename: Josette
authors.initials: J
authors.lastname: Derré
authors.forename: Jérome
authors.initials: J
authors.lastname: Couturier
authors.forename: Alain
authors.initials: A
authors.lastname: Aurias
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D019457:Chromosome Breakage / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003116:Color; D004261:DNA Replication; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D008677:Metaphase; D009447:Neuroblastoma / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods*; D014178:Translocation, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured