Loss in chromosome 11q identifies tumors with increased risk for metastatic relapses in localized and 4S neuroblastoma.
OBJECTIVE
To improve risk prediction in neuroblastoma and to specify the type of a possible relapse, alterations in the long arm of chromosome 11 were analyzed.


METHODS
A representative cohort of 611 neuroblastomas was investigated for deletion events in distal chromosome 11q using interphase fluorescence in situ hybridization.


RESULTS
Alterations in 11q were found in 159 of 611 tumors in the whole cohort (26%) and were associated with stage 4 disease (P < 0.001) and age at diagnosis of >2.5 years (P < 0.001). Event-free survival and overall survival were significantly poorer for patients with 11q loss in the whole cohort (event-free survival and overall survival, P < 0.001) and in different subsets: neuroblastoma without MYCN amplification (MNA) (event-free survival and overall survival, P < 0.001), with MNA (event-free survival, P = 0.03; overall survival, P = 0.02), and MYCN-nonamplified stage 1, 2, 3, and 4S tumors with and without del 1p (event-free survival and overall survival, P < 0.001). In stage 4, the 11q status did not discriminate outcome. By multivariate analysis, the 11q status proved prognostic for event-free survival in the whole cohort (P = 0.008; hazard ratio, 1.573) and in the subgroup of stages 1, 2, 3, and 4S without MNA (P < 0.001; hazard ratio, 3.534). Moreover, 11q alterations were strongly correlated with the occurrence of metastatic relapses (P < 0.001).


CONCLUSIONS
In addition to the current risk stratification, the status of 11q enables the identification of patients with an increased risk for relapses in general and metastatic relapses in particular.
Spitz
Ruediger
R
Authors' Affiliations: Department of Pediatric Oncology, University Children's Hospital, Köln, Germany. Ruediger.Spitz@uk-koeln.de
Hero
Barbara
B
Simon
Thorsten
T
Berthold
Frank
F
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015331:Cohort Studies; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome