Gain of distal chromosome arm 17q is not associated with poor prognosis in neuroblastoma.
OBJECTIVE
In several studies, gain of the distal long arm of chromosome 17 was shown to be a frequent and prognostically relevant factor in neuroblastoma, in addition to MYCN amplification (MNA) or 1p deletion. We asked whether this observation could be confirmed in a German cohort.


METHODS
To evaluate the frequency and prognostic impact of 17q gain, we investigated tissue samples from 193 neuroblastoma patients by the use of fluorescence in situ hybridization. The DNA probe (MPO) was located in distal 17q in the region of interest as used by several groups. To analyze the association of patients' outcome with the breakpoint position within 17q, we used the more proximal DNA probe ERBB2 in 17q21 on a selected number of cases. Gain was defined as an excess of 17q material compared with the chromosome 17 centromere in at least 50% of the analyzed tumor cells. In addition, alterations in chromosomes 1p, 3p, and 11q, as well as MYCN status, were determined to describe the interrelationship between the different parameters and to evaluate an independent prognostic influence.


RESULTS
Gain of 17q was found in 61% of the investigated tumors. An additional 23% displayed an excess of 17q in less than half of all cells. Gain correlated with stage 4 disease (P = 0.003) and with other chromosomal alterations, such as 1p (P < 0.001), 3p (P = 0.01), 11q (P = 0.001), and MNA (P = 0.016), as well as with increased patient age (P = 0.01). Outcome was not different between patients with 17q gain compared with those without, however. A prognostic influence could not be delineated in all stages or in localized or in stage 4 subgroups or in the MYCN nonamplified patient cohort. Outcome did not differ between patients with additional 17q material in <10% of the cells or in >70%. Patients showing a breakpoint in the more proximal part of 17q could not be described as having a more favorable outcome compared with patients with a more distal breakpoint. Prognosis was poor in patients with MNA and/or 11q loss either with or without 17q gain. A multivariate analysis including the chromosomal parameters 17q, 11q, and MYCN status, as well as stage, showed MYCN and 11q status (P < 0.001), but not 17q or stage as significant prognostic factors.


CONCLUSIONS
Although the most frequent aberration in neuroblastoma to date, we found no association between 17q gain and an inferior prognosis in our cohort; the status of MYCN and 11q, however, allowed reliable prediction of patients' outcomes.
Spitz
Ruediger
R
University of Cologne, Children's Hospital, Pediatric Oncology, 50924 Köln, Germany. Ruediger.Spitz@medizin.uni-koeln.de
Hero
Barbara
B
Ernestus
Karen
K
Berthold
Frank
F
D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015999:Multivariate Analysis; D009447:Neuroblastoma / Q000175:diagnosis* / Q000235:genetics*; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
D004247:DNA