PARTIAL DELETIONS OF THE CDKN2 AND MTS2 PUTATIVE TUMOR-SUPPRESSOR GENES IN A MYXOID CHONDROSARCOMA

Cytogenetic abnormalities of chromosome 9 (9p21) have been reported in a large number of tumors that include malignant melanomas, gliomas, l ung cancers and leukemias. These aberrations on 9p have been previousl y shown to involve the loss of the interferon gene cluster and the gen e for methylthioadenosine phosphorylase (MTAP), both of which have bee n mapped to the 9p21 region. Recently, two putative tumor suppressor g ene(s) CDKN2 and MTS2, have been mapped tb the 9p21 region, and have b een shown to be deleted in a large number of hematopoietic and solid m alignancies. In this study we report a cytogenetic and a detailed mole cular analysis of a myxoid chondrosarcoma cell line 105KC and its clon al derivatives 105AJ, 105AJ1.1, 105AJ3.1, and 105AJ5.1. Specifically, we have demonstrated chromosome 9p21 related abnormalities by cytogene tic analysis, the associated loss of the interferon gene cluster, and the loss of the immunoreactive MTAP protein and activity. In addition, we have also shown the presence of deletions involving the CDKN2 and the MTS2 putative tumor suppressor genes in these chondrosarcoma cell lines. The above studies were extended to other chondrosarcoma cell,li nes and primary tumors, where similar deletions of the CDKN2 and MTS2 genes were found to be present (unpublished data). This suggests a pot ential role for the involvement of the CDKN2 and MTS2 putative tumor s uppressor genes in the development of chondrosarcomas.