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

Abstract

Loss of heterozygosity (LOH) on chromosome arm 17p is the most common genetic aberration in childhood primitive neuroectodermal tumors (PNETs). To determine the frequency and extent of 17p deletions, 29 loci on 17p were investigated in 24 tumors by using restriction fragment length polymorphism (RFLP) and microsatellite analysis. LOH on 17p was found in 9 of 24 tumors. In all tumors with LOH, a continuous stretch from 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 deletion breakpoint on the cytogenetic map of chromosome 17 and to exclude uniparental disomy, we verified our data by using fluorescence in situ hybridization (FISH) analyses. By using two yeast artificial chromosome (YAC) clones that were positive for D17S689 and D17S953, the same breakpoint was confirmed in two specimens of cerebrospinal fluid (CSF) metastases by using FISH on interphase preparations. We demonstrate that, in most childhood PNETs with LOH on 17p, the breakpoint is close to, but not within, the centromere. It varies, and it occurs predominantly between the two markers D17S689 and D17S953, which is an unstable chromosomal region that is deleted or duplicated in the Smith‐Magenis syndrome. Because LOH of 17p is associated with the formation of isochromosome 17q in the majority of PNETs, this study provides entry points to determine the molecular nature of this phenomenon. Genes Chromosom. Cancer 18:50–58, 1997. © 1997 Wiley‐Liss, Inc.

Aberrant promoter methylation of previously unidentified target genes is a common abnormality in medulloblastomas–Implications for tumor biology and potential clinical utility

“…INK4A is an integral part of the RB pathway and loss of 17p, the location of TP53, is a frequent event in medulloblastomas (Scheurlen et al, 1997). It is thus tempting to speculate that a subset of medulloblastomas might be caused by a combination of defects in both, the TP53 and the RB, pathways.…”

Comparative genomic hybridization detects many recurrent imbalances in central nervous system primitive neuroectodermal tumours in children

“…Nevertheless, some patients have only gain of 17q and others have only loss of 17p, suggesting that these two abnormalities may involve different tumorigenic pathways. Recent data showed that different regions may be lost in 17p deletions, leading to the loss of different putative tumour suppressor genes (Biegel et al, 1992;Cogen et al, 1992;McDonald et al, 1994;Batra et al, 1995;Scheurlen et al, 1997). On the other hand, gain of chromosome 17q (through the formation of an isochromosome or an isolated gain of 17q) is probably an important second event, by modifying some gene dosage.…”

“…Other studies using molecular approaches confirmed this frequent loss of 17p, and localized a hot-spot of loss of heterozygosity at 17p13.3, a locus telomeric to the p53 gene (Biegel et al, 1992;Cogen et al, 1992;McDonald et al, 1994;Batra et al, 1995). A very recent deletion mapping study localized a common chromosomal disruption within a more centromeric region, at 17p11.2 (Scheurlen et al, 1997). Other recurrent abnormalities have been described, including structural aberrations of chromosomes 1, 3, 6, 11, 16 and X, loss of chromosome 22 and gains of chromosomes 6 and 8 (Farwell et al, 1977;Bigner et al, 1988Bigner et al, , 1990Griffin et al, 1988;Callen et al, 1989;Karnes et al, 1992;Neumann et al, 1993;Fujii et al, 1994).…”

Interphase FISH screening for the LCR-mediated common rearrangement of isochromosome 17q in primary myelofibrosis

“…Although it is not known whether i(17q) can initiate the primary events causing malignancy, studies suggest that it can confer clonal advantage to tumor cells [19]. Mapping the i(17q) breakpoint in a number of malignancies has identified i(17q) as an isodicentric abnormality in the majority of cases [19][20][21]. However, other hematological disorders that may contain i(17q), among them myeloproliferative disorders, have not been associated with the presence of the dicentric anomaly.…”