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Previous Volume 340:1954-1961 June 24, 1999 Number 25 Next

Nick Bown, M.Sc., Simon Cotterill, B.A., Maria astowska, M.D., Ph.D., Seamus O'Neill, Ph.D., Andrew D.J. Pearson, M.D., Dominique Plantaz, M.D., Mounira Meddeb, M.D., Ph.D., Gisele Danglot, M.D., Christian Brinkschmidt, M.D., Holger Christiansen, M.D., Genevieve Laureys, M.D., Ph.D., Frank Speleman, Ph.D., James Nicholson, M.B., B.Chir., Alain Bernheim, M.D., David R. Betts, B.Sc., Jo Vandesompele, Ph.D., and Nadine Van Roy, Ph.D.

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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 compiled 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 factor, 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.

Source Information

From the Department of Human Genetics (N.B., M.., S.O.) and the Institute of Child Health (S.C., A.D.J.P.), University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; the Department of Pediatrics, University Hospital Center, Grenoble, France (D.P.); Institut Gustave-Roussy, Villejuif, France (M.M., G.D.); Gerhard-Domagk Institute of Pathology, University of Munster, Munster, Germany (C.B.); the Department of Pediatric Hematology and Oncology, Kinderklinik, University of Marburg, Marburg, Germany (H.C.); and the Department of Pediatric Oncology (G.L.) and the Center for Medical Genetics (F.S.), University Hospital, Ghent, Belgium. Other authors were James Nicholson, M.B., B.Chir., University of Southampton, Southampton, United Kingdom; Alain Bernheim, M.D., Institut Gustave-Roussy, Villejuif, France; David R. Betts, B.Sc., University Children's Hospital, Zurich, Switzerland; and Jo Vandesompele, Ph.D., and Nadine Van Roy, Ph.D., University Hospital, Ghent, Belgium.

Address reprint requests to Mr. Bown at the Department of Human Genetics, University of Newcastle upon Tyne, 19-20 Claremont Pl., Newcastle upon Tyne NE2 4AA, United Kingdom, or at nicholas.bown{at}ncl.ac.uk.

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