CYTOGENETIC ANALYSIS OF SOFT-TISSUE SARCOMAS - RECURRENT CHROMOSOME-ABNORMALITIES IN MALIGNANT PERIPHERAL-NERVE SHEATH TUMORS (MPNST)

Malignant peripheral nerve sheath tumors (MPNST) are known to develop in patients with neurofibromatosis 1 (NF1), thus providing an excellen t model for the study of multistep carcinogenesis in genetically predi sposed individuals. To determine the sites of gene(s) involved in such a process, we have performed cytogenetic analysis on 10 tumors. The p atients were five males and five females ranging in age from 15 to 77 years. Nine patients had NF1. Karyotypic analysis of these tumors exhi bited complex clonal abnormalities of several chromosomes. Recurrent a bnormalities (numerical as well as structural) of chromosomes 1, 11, 1 2, 14, 17, and 22 occurred in a substantial proportion of tumors studi ed. Although abnormalities of these chromosomes have been seen in a va riety of other tumors, the aberrations of chromosomes 17 and 22 are of particular interest; chromosomes 17 and 22 carry the genes for NF1 an d NF2, respectively. In addition to other clonal aberrations, six tumo rs had abnormalities of both chromosomes 17 and 22, while three tumors only had an abnormality of chromosome 17. In eight tumors a structura l abnormality of chromosome 17 included deletion or a relative deficie ncy of 17p; in four of the tumors there was also either deletion or re arrangement of the NF1 locus at the cytogenetic level. One tumor had m onosomy of chromosome 17. The abnormality of chromosome 22 was deletio n of 22q11.2-->qter. This study suggests that the germline mutation in one of the copies accompanied by loss or inactivation of the second c opy of the NF1 gene and tumor suppressor gene(s) on 17p and 22q may be associated with the neoplastic transformation; abnormalities of other chromosomes may be related to progression of MPNST. Although the role of the p53 gene in carcinogenesis is well documented in several tumor types, the role of the NF2 gene or other unidentified tumor suppresso r gene(s) on chromosomes 22q, Ip, 11, 12, 14 remains to be seen.