Molecular characterization of a 17q11.2 translocation in a malignant schwannoma cell line

Abstract

Malignant schwannomas are soft-tissue neoplasms that occur at increased frequency with germline alterations of the neurofibromatosis-1 (NF1) gene at 17q11.2. We report molecular and cytogenetic characterization of a malignant schwannoma cell line established from an individual affected with NF1. This cell line has a complex hyperdiploid karyotype with two cytogenetically identical der(13)t(13;17)(p11,q11.2) chromosomes. Using somatic cell hybrids, we mapped twelve chromosome-17 probes to either the der(13)t(13;17) chromosome or a small der(17) chromosome. Two chromosome-17p loci, including the p53 tumor suppressor gene, were present in the schwannoma cell line, but did not map to either of these chromosomes. Loss of heterozygosity studies indicated that the two der(13)t(13;17) chromosomes arose by duplication, presumably after the translocation event. The 17q11.2 translocation break-point maps distal to the NF1 gene, and may not disrupt its functioning. Although NF1 mRNA was detected in this cell line by polymerase chain reaction, Northern blot analysis revealed very little or none of the 13-kb mature NF1 transcript. This suggests that the single remaining allele of the NF1 gene contains a mutation that results in either greatly reduced transcription or message instability.

The Ras Inhibitor Farnesylthiosalicylic Acid as a Potential Therapy for Neurofibromatosis Type 1

“…These allelotyping results show that the cell lines originate from monoclonal tumors, but despite their monoclonality, there seems to be a residual DNA contribution from a non tumorous tissue, as evident from the minimal signal of the ''lost allele.'' In this regard, it is worth noting that a 17q11.2 translocation has been characterized previously in a MPNST cell line (33) and that recombination hotspot in NF1 microdeletion patients has been characterized as well (35).…”

“…We assume that the ST88-14 cell line contains a pathogenic inactivating mutation, as yet undetected. In fact, this cell line was shown previously to contain a karyotypically complex gene rearrangement involving 17q and to display allelic loss of 17q (33).…”

Large-Scale Molecular Comparison of Human Schwann Cells to Malignant Peripheral Nerve Sheath Tumor Cell Lines and Tissues

“…No mutations were detected in the coding region of the NF1 gene in either sporadic MPNST sample (data not shown). Loss of heterozygosity (LOH) at the NF1 locus has previously been confirmed in five of the six NF1-associated MPNST lines (8,25,26).…”

STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications

“…Over a 5 day period, GIST882 proliferation was consistently inhibited by STI571 concentrations 50.1 mM (Figure 2). In contrast, cell proliferation was not inhibited by even 10 mM STI571 in any of the four comparison sarcoma cell lines, including the malignant peripheral nerve sheath tumor cell line ST88-014 (Figure 2, Reynolds et al, 1992), the ®brosarcoma cell line HT-1080 (not shown, Rasheed et al, 1974), and immortal cell lines established from malignant peripheral nerve sheath tumors and mesotheliomas (data not shown). Although ST88-014 has been reported to express c-KIT and respond to exogeneous SCF (Badache et al, 1998), we did not supplement the cultures with SCF and therefore could not determine whether STI571 inhibits the KIT/SCF pathway in MPNST 88-014.…”