EVIDENCE FOR 2 TUMOR-SUPPRESSOR LOCI ON CHROMOSOMAL BANDS-1P35-36 INVOLVED IN NEUROBLASTOMA - ONE PROBABLY IMPRINTED, ANOTHER ASSOCIATED WITH N-MYC AMPLIFICATION

Previous reports on possible genomic imprinting of the neuroblastoma t umour suppressor gene on chromosome 1p36 have been conflicting. Here w e report on the parental origin of 1p36 alleles lost in 47 neuroblasto mas and on a detailed Southern blot analysis of the extent of the 1p d eletions in 38 cases, The results are remarkably different for tumours with and without N-myc amplification. In the N-myc single copy tumour s we show that the lost 1p36 alleles are of preferential maternal orig in (16 of 17 cases) and that the commonly deleted region maps to 1p36. 2-3, In contrast, all N-myc amplified neuroblastomas have larger 1p de letions, extending from the telomere to at least 1p35-36.1. These dele tions are of random parental origin (18 of 30 maternal LOH). This stro ngly suggests that different suppressor genes on 1p are inactivated in these two types of neuroblastoma. Deletion of a more proximal suppres sor gene is associated with N-myc amplification, while a distal, proba bly imprinted, suppressor can be deleted in N-myc single copy cases.