FREQUENT SOMATIC MUTATIONS AND HOMOZYGOUS DELETIONS OF THE P16 (MTS1)GENE IN PANCREATIC ADENOCARCINOMA

The MTS1 gene on chromosome 9p21 encodes the p16 inhibitor of cyclinD/ Cdk-4 complexes, and is deleted or mutated in a variety of tumour type s. We found allelic deletions of 9p21-p22 in 85% of pancreatic adenoca rcinomas. Analysis of MTS1 in pancreatic carcinomas (27 xenografts and 10 cell lines) showed homozygous deletions in 15(41%) and sequence ch anges in 14 (38%). These included eight point mutations (four nonsense , two missense and two splice site mutations) and six deletions/ inser tions, all accompanied by loss of the wild-type allele. Sequencing of MTS1 from primary tumours confirmed the mutations. Coexistent inactiva tions of both MTS1 and p53 was common and suggests that abnormal regul ation of cyclin-dependent kinases may play an important role in the bi ology of pancreatic carcinoma.