Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma

Background Gain of genetic material from chromosome arm 17q (gain of segmen t 17q21-qter) is the most frequent cytogenetic abnormality of neuroblastoma cells. This gain has been associated with advanced disease, patients who a re greater than or equal to 1 year old, deletion of chromosome arm 1p, and amplification of the N-myc oncogene, all of which predict an adverse outcom e. We investigated these associations and evaluated the prognostic importan ce of the status of chromosome 17. Methods We compiled molecular cytogenetic analyses of chromosome 17 in prim ary neuroblastomas in 313 patients at six European centers. Clinical and su rvival information were collected, along with data on 1p, N-myc, and ploidy . Results Unbalanced gain of segment 17q21-qter was found in 53.7 percent of the tumors, whereas the chromosome was normal in 46.3 percent. The gain of 17q was characteristic of advanced tumors and of tumors in children greater than or equal to 1 year of age and was strongly associated with the deleti on of 1p and amplification of N-myc. No tumor showed amplification of N-myc in the absence of either deletion of 1p or gain of 17q. Gain of 17q was a significant predictive factor for adverse outcome in univariate analysis. A mong the patients with this abnormality, overall survival at five years was 30.6 percent (95 percent confidence interval, 21 to 40 percent), as compar ed with 86.0 percent (95 percent confidence interval, 78 to 91 percent) amo ng those with normal 17q status. In multivariate analysis, gain of 17q was the most powerful prognostic factor, followed by the presence of stage 4 di sease and deletion of 1p (hazard ratios, 3.4, 2.3, and 1.9, respectively). Conclusions Gain of chromosome segment 17q21-qter is an important prognosti c factor in children with neuroblastoma. (N Engl J Med 1999;340:1954-61.) ( C) 1999, Massachusetts Medical Society.