Summary Neuroblastoma is the most common extracranial solid tumour of childhood. Amplification of the proto-oncogene, N-myc, confers a poor prognosis in neuroblastoma, while hyperdiploidy is associated with a favourable outcome. Little is known about the contribution of tumour-suppressor genes to the development or progression of neuroblastoma. We examined allelic imbalance at the locus of the tumour-suppressor gene, APC (adenomatous polyposis coli), on chromosome 5q using a polymerase chain reaction (PCR)-based assay. Nine of 24 (37.5%) informative neuroblastoma tumours showed allelic imbalance (Al) at this locus. Clinical data concerning N-myc amplification and DNA content were correlated with these results in the same patients. Allelic imbalance was found only in tumours containing a single copy of the N-myc gene and exhibiting hyperdiploidy. All nine patients with Al of chromosome 5q were alive after a median follow-up period of 46 months, while 7 of 15 (47%) of those lacking Al at this locus had died (P=0.018). Allelic imbalance at three additional loci on chromosome 5 was demonstrated in tumours that exhibited Al at the APC locus, suggesting that endoreduplication of chromosome 5 had occurred. Fluorescent in situ hybridisation (FISH) analysis of tumour tissue from one patient exhibiting AI demonstrated two, three, four or six copies of the APC gene per cell, consistent with this hypothesis. These data suggest that allelic imbalance of chromosome 5 is involved in at least a subset of neuroblastomas and influences survival in patients with neuroblastoma.

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The murine IgG2a monoclonal antibody 6–19 binds to a wide variety of nonhematopoietic cells including human marrow-derived stromal cells but does not bind to marrow or peripheral blood cells. We studied the effects of this antibody and rabbit complement on marrow cells. Fibroblast colonies were eliminated from light density marrow cells by a single incubation with monoclonal antibody 6–19 and complement. The growth and composition of granulocytic and erythroid colonies were unaffected. Specific complement mediated cytotoxicity of the antibody was confirmed on passaged human fibroblasts derived from marrow (more than 99.6% of fibroblasts are killed by a single treatment). Similar results were obtained with human umbilical cord endothelial cells. In addition, such treatment abolished the initiation of Dexter culture stroma. Incubation of bone marrow cell suspensions with this antibody and complement will allow the study of stroma-free marrow cells in long- term liquid cultures.