title: Molecular cytogenetic analysis of recurrent unbalanced t(11;17) in neuroblastoma.
abstract: Loss of 11q material occurs in approximately 30% of advanced stage neuroblastoma and defines a distinct genetic subtype of this disease. These tumors almost always possess unbalanced gain of the 17q, along with many additional recurrent chromosomal imbalances. Loss of 11q and gain of 17q is often the consequence of an unbalanced translocation between the long arms of both chromosomes, but because of the involvement of other chromosomal mechanisms, the actual frequency of t(11;17) is unknown. In addition, chromosomal breakpoint positions for the t(11;17) are variable in different tumors, with breakpoints on neither the 11q nor 17q being well defined. We have used interphase fluorescence in situ hybridization analysis to detect a der(11)t(11;17) in a series of neuroblastomas with 11q loss/17q gain using a statistical approach which could be applicable to the detection of translocations in other solid tumors. The frequency of der(11)t(11;17) was approximately 90% in our neuroblastoma series. A balanced t(11;17) was also detected in a MYCN amplified tumor, which is a distinctly different genetic subtype from the 11q- tumors. Breakpoint positions on 11q were determined to be variable, whereas all breakpoints on 17q appeared to cluster proximal to position 43.1 Mb on the DNA sequence map. The majority of tumors had large numbers of nuclei with 2 or more copies of der(11)t(11;17), which led to unbalanced gain of 11p, and further increases in 17q imbalance. The prevalence of t(11;17) in neuroblastoma warrants additional studies to further define the range in variation in breakpoint positions on both chromosomes and to elucidate the molecular mechanisms that lead to this important and interesting recurrent genetic abnormality.
authors.affiliation: National Centre for Medical Genetics Our Lady's Hospital for Sick Children Crumlin, Dublin 12, Ireland. stallings@uthscsa.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Stallings
authors.forename: P
authors.initials: P
authors.lastname: Carty
authors.forename: L
authors.initials: L
authors.lastname: McArdle
authors.forename: M
authors.initials: M
authors.lastname: Mullarkey
authors.forename: M
authors.initials: M
authors.lastname: McDermott
authors.forename: F
authors.initials: F
authors.lastname: Breatnach
authors.forename: A
authors.initials: A
authors.lastname: O'Meara
mesh_terms: D022202:Chromosomes, Artificial, Bacterial; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009447:Neuroblastoma / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods; D014178:Translocation, Genetic