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

Lookup NU author(s): Dr Nicholas Bown, Simon Cotterill, Dr Maria Lastowska, Dr Seamus O'Neill, Professor Andrew Pearson

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Abstract

Background: Gain of genetic material from chromosome arm 17q (gain of segment 17q21-qter) is the most frequent cytogenetic abnormality of neuroblastoma cells. This gain has been associated with advanced disease, patients who are ≥1 year old, deletion of chromosome arm 1p, and amplification of the N-myc oncogene, all of which predict an adverse outcome. We investigated these associations and evaluated the prognostic importance of the status of chromosome 17. Methods: We complied molecular cytogenetic analyses of chromosome 17 in primary neuroblastomas in 313 patients at six European centers. Clinical and survival 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 ≥1 year of age and was strongly associated with the deletion 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. Among the patients with this abnormality, overall survival at five years was 30.6 percent (95% percent confidence interval, 21 to 40 percent), as compared with 86.0 percent (95 percent confidence interval, 78 to 91 percent) among those with normal 17q status. In multivariate analysis, gain of 17q was the most powerful prognostic factors, followed by the presence of stage 4 disease and deletion of 1p (hazard ratios, 3.4, 2.3, and 1.9, respectively). Conclusions: Gain of chromosome segment 17q21-qter is an important prognostic factor in children with neuroblastoma.


Publication metadata

Author(s): Bown N, Cotterill S, Lastowska M, O'Neill S, Pearson ADJ, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, Laureys G, Speleman F, Nicholson J, Bernheim A, Betts DR, Vandesomple J, Van Roy N

Publication type: Article

Publication status: Published

Journal: New England Journal of Medicine

Year: 1999

Volume: 340

Issue: 25

Pages: 1954-1961

Print publication date: 01/01/1999

ISSN (print): 0028-4793

ISSN (electronic): 1533-4406

Publisher: Massachusetts Medical Society

URL: http://dx.doi.org/10.1056/NEJM199906243402504

DOI: 10.1056/NEJM199906243402504

PubMed id: 10379019


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