HIGH-RESOLUTION DELETION MAPPING OF CHROMOSOME ARM 17P IN CHILDHOOD PRIMITIVE NEUROECTODERMAL TUMORS REVEALS A COMMON CHROMOSOMAL DISRUPTION WITHIN THE SMITH-MAGENIS REGION, AN UNSTABLE REGION IN CHROMOSOME BAND 17P11.2

Loss of heterozygosity (LOH) on chromosome arm 17p is the most common genetic aberration in childhood primitive neuroectodermal tumors (PNET s). To determine the frequency and extent of 17p deletions, 29 loci on 17p were investigated in 24 tumors by using restriction fragment leng th polymorphism (RFLP) and microsatellite analysis. LOH on 17p was fou nd in 9 of 24 tumors. In all tumors with LOH, a continuous stretch fro m the telomere to chromosome band 17p11.2 was completely deleted, and no interstitial or terminal small-scale deletions were detected in the remaining 15 tumors. In four tumors with LOH on 17p, the chromosomal breakpoint was located between D17S953 and D17S805. To identify this d eletion breakpoint on the cytogenetic map of chromosome 17 and to excl ude uniparental disomy, we verified our data by using fluorescence in situ hybridization (FISH) analyses. By using two yeast artificial chro mosome (YAC) clones that were positive for D17S689 and D17S953, the sa me breakpoint was confirmed in two specimens of cerebrospinal fluid (C SF) metastases by using FISH on interphase preparations. We demonstrat e that, in most childhood PNETs with LOH on 17p, the breakpoint is clo se to, but not within, the centromere. It varies, and it occurs predom inantly between the two markers D17S689 and D17S953, which is an unsta ble chromosomal region that is deleted or duplicated in the Smith-Mage nis syndrome. Because LOH of 17p is associated with the formation of i sochromosome 17q in the majority of PNETs, this study provides entry p oints to determine the molecular nature of this phenomenon. (C) 1997 W iley-Liss, Inc.