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.