MTS1/CDKN2 gene mutations are rare in primary human astrocytomas with allelic loss of chromosome 9p

Human astrocytomas frequently have allelic losses of chromosome9p, suggesting the presence of a 9p astrocytoma tumor suppressorgene. The MTS1 (or CDKN2) gene on chromosome 9p encodes a cell-cycleregulator and is deleted in approximately 80% of astrocytomacell lines. To determine whether MTS1 is the tumor suppressorgene involved in human astrocytoma formation in vivo, we haveanalyzed chromosome 9p allelic loss and the MTS1 gene in 30primary astrocytomas. Deletion mapping demonstrated 15 caseswith allelic loss of chromosome 9p, with all losses either flankingor involving the MTS1 gene. Direct analysis of the MTS1 gene,however, revealed only a single missense mutation in a high-gradetumor that had lost the second allele. The low frequency ofMTS1 mutations in primary astrocytomas with allelic 9p losssuggests that MTS1 may be more important for in vitro than invivo astrocytoma growth, and that another 9p tumor suppressorgene may be involved in astrocytoma formation in vivo. Analysisof the MTS1 gene also demonstrated two intragenic polymorphisms,one in exon 2 and one in the 3' untranslated region, that canbe used to assay allelic loss directly at MTS1.