2 DISTINCT DELETED REGIONS ON THE SHORT ARM OF CHROMOSOME-I IN NEUROBLASTOMA

The short arm of chromosome 1p is the most frequently altered chromoso me segment in neuroblastoma. The alterations, mainly deletions, are th ought to be indicative of the presence of a tumor suppressor gene. To further refine the chromosome localization of this gene, we have studi ed paired constitutional and tumor DNA from a series of 60 patients wi th neuroblastoma at 2 minisatellite and 23 microsatellite loci dispers ed along the short arm of chromosome 1. Twenty-two cases (37%) demonst rated loss of heterozygosity (LOH) at one or more loci on 1p. Surprisi ngly, the pattern of LOH enabled the identification of two distinct co nsensus regions of deletions. In agreement with previous reports, one region mapped to the distal short arm of chromosome 1. The other regio n was localized more proximally on 1 p. Deletions observed in tumors i nvolve either one or both of these regions. We show that the correlati on between NMYC amplification and 1p deletion is limited to the deleti ons which involve the proximal region either alone or together with th e distal region. These results suggest that two tumor suppressor genes on 1p might be involved in the development of neuroblastoma. Finally, we show that somatic mutations at microsatellite loci, frequently obs erved in other types of cancer, are rare events in neuroblastoma. Gene s Chromosom Cancer 10:275-281 (1994). (C) 1994 Wiley-Liss, Inc.