Nature Genetics
8, 27 - 32 (1994)
doi:10.1038/ng0994-27
Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinomaCarlos Caldas1, Stephan A. Hahn2, Luis T. da Costa4, Mark S. Redston2, Mieke Schutte2, Albert B. Seymour2, Craig L. Weinstein2, Ralph H. Hruban2, Charles J. Yeo3
& Scott E. Kern1, 2, 5
1Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
2Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
3Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
4The Division of Toxicology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA
5Correspondence should be addressed to S.E.K. 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 types. We found allelic deletions of 9p21−p22 in 85% of pancreatic adenocarcinomas. Analysis of MTS1 in pancreatic carcinomas (27 xenografts and 10 cell lines) showed homozygous deletions in 15 (41%) and sequence changes in 14 (38%). These included eight point mutations (four nonsense, two missense and two splice site mutations) and six deletions/ insertions, all accompanied by loss of the wild-type allele. Sequencing of MTS1 from primary tumours confirmed the mutations. Coexistent inactivations of both MTS1 and p53 was common and suggests that abnormal regulation of cyclin-dependent kinases may play an important role in the biology of pancreatic carcinoma.
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