Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.

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