MTS-1 (CDKN2) TUMOR-SUPPRESSOR GENE DELETIONS ARE A FREQUENT EVENT INESOPHAGUS SQUAMOUS CANCER AND PANCREATIC ADENOCARCINOMA CELL-LINES

MTS-1 is a candidate tumor suppressor gene on chromosome 9p21-22, a re gion frequently observed to have loss of heterozygosity in esophagus s quamous cell carcinomas and pancreatic ductal adenocarcinomas. In orde r to determine whether MTS-1 sequences are deleted or mutated in cell lines derived from these cancers, we performed PCR amplification of MT S-1 exons 1 and 2. In this fashion, we found that 67% of esophagus squ amous cancer cell lines have deletions of both exons 1 and 2, and 50% of pancreatic cancer cell lines have similar deletions. Furthermore, a n additional 30% of pancreatic cancer cell lines harbored point mutati ons or microdeletions based on DNA sequencing. MTS-1 encodes p16, an i nhibitor of cyclin-dependent kinase 4 (cdk4) which complexes with cycl in D1. Our data suggest that MTS-1 deletions and mutations may play an important role in the molecular pathogenesis of esophagus squamous ce ll and pancreatic cancers.