A CELL-CYCLE REGULATOR POTENTIALLY INVOLVED IN GENESIS OF MANY TUMOR TYPES

A putative tumor suppressor locus on the short arm of human chromosome 9 has been localized to a region of less than 40 kilobases by means o f homozygous deletions in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously i dentified inhibitor (pl 6) of cyclin-dependent kinase 4. MTS1 was homo zygously deleted at high frequency in cell lines derived from tumors o f lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphoc yte. Melanoma cell lines that carried at least one copy of MTS1 freque ntly carried nonsense, missense, or frameshift mutations in the gene. These findings suggest that MTS1 mutations are involved in tumor forma tion in a wide range of tissues.