ALLELIC LOSS OF CHROMOSOME 1P AS A PREDICTOR OF UNFAVORABLE OUTCOME IN PATIENTS WITH NEUROBLASTOMA

Background. Neuroblastoma is a childhood tumor derived from cells of t he neural crest, with a widely variable outcome. Differences in the be havior and prognosis of the tumor suggest that neuroblastoma can be di vided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in neuroblastoma to determine their prognostic v alue. Methods. We used Southern blot analysis to study the allelic los s of chromosomes 1p, 4p, 11q, and 14q, the duplication of chromosome 1 7q, and the amplification of the N-myc oncogene in 89 neuroblastomas. We also determined the nuclear DNA content of the tumor cells. Results . Allelic loss of chromosome 1p, N-myc amplification, and extra copies of chromosome 17q were significantly associated with unfavorable outc omes. In a multivariate analysis, loss of chromosome Ip was the most p owerful prognostic factor. It provided strong prognostic information w hen it was included in multivariate models containing the prognostic f actors of age and stage or serum ferritin level and stage. Among the p atients with stage I, II, or IVS disease, the mean (+/-SD) three-year event-free survival was 100 percent in those without allelic loss of c hromosome Ip and 34 +/- 15 percent in those with such loss; the rates of three-year event-free survival among the patients with stage III an d stage IV disease were 53 +/- 10 percent and 0 percent, respectively. Conclusions. The loss of chromosome 1p is a strong prognostic factor in patients with neuroblastoma, independently of age and stage. It rel iably identifies patients at high risk in stages I, II, and IVS, which are otherwise clinically favorable. More intensive therapy may be con sidered in these patients. Patients in stages III and IV with allelic loss of chromosome 1p have a very poor outlook, whereas those without such loss are at moderate risk. (C) 1996, Massachusetts Medical Societ y.