ALLELIC LOSS OF THE SHORT ARM OF CHROMOSOME-4 IN NEUROBLASTOMA SUGGESTS A NOVEL TUMOR-SUPPRESSOR GENE LOCUS

Neuroblastoma is a childhood neural crest tumour, genetically characte rized by frequent deletions of the short arm of chromosome 1 and ampli fication of N-myc. Here we report the first evidence for a neuroblasto ma tumour suppressor locus on 4pter. Cytogenetically we demonstrated r earrangements of 4p in 7 out of 26 evaluable tumours (27%). Subsequent analysis of loss of heterozygosity (LOH) by Southern blotting reveale d allelic loss of 4p in 16/82 (19.5%) informative neuroblastomas. Take n together cytogenetic and Southern blot analyses showed loss of 4p in 20/86 neuroblastomas analysed (23%). The common delete region was bor dered by the probe D4S123 and encompassed the distal 34 cM of 4p. We f ound no evidence for genomic imprinting of the 4p locus as the 4p alle les lost in the tumours were of random maternal and paternal origin. L OH4p was found at all disease stages and in every age group. Furthermo re LOH4p was present both in cases with and without LOH1p and amplific ation of N-myc.