Variety and complexity of chromosome 17 translocations in neuroblastoma.
In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm 17q, which arises from unbalanced translocations. To document these genetic events more precisely, we performed an extensive study of chromosome 17 breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence in situ hybridization mapping with BAC/PAC clones and allele analysis with polymorphic markers. All cases exhibited one or more unbalanced chromosome 17 translocations, and 15 distinct breakpoint regions could be mapped. This high variability indicates that gene fusion or disruption events are extremely unlikely to account for the underlying oncogenic role of these translocations. However, breakpoints were not randomly distributed, most of them mapping to the proximal part of 17q. As a result of translocations, all cell lines but one exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10, defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition to chromosome gains, loss of heterozygosity for the short arm of chromosome 17 was observed in close to half the cases. It was either related to a chromosome 17 monosomy or to a uniparental isodisomy. Finally, in cases with a single normal chromosome 17, we show that the parental origin of the translocated chromosome 17 can be either distinct or identical to that of the normal chromosome. Similarly, multiple translocations within the same cell line can either involve the same or different chromosome 17 homologues, indicating the likely absence of parental origin bias in the generation of these alterations.
Schleiermacher
Gudrun
G
INSERM Unité 509, Laboratoire de Pathologie Moléculaire des Cancers, Institut Curie, Paris, France.
Raynal
Virginie
V
Janoueix-Lerosey
Isabelle
I
Combaret
Valérie
V
Aurias
Alain
A
Delattre
Olivier
O
D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000706:statistics & numerical data; D020223:Chromosome Painting / Q000379:methods; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D006801:Humans; D007621:Karyotyping / Q000379:methods; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics*