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

Carlos Caldas, Stephan A. Hahn, Luis T. Da-Costa, Mark S. Redston, Mieke Schutte, Albert B. Seymour, Craig L. Weinstein, Ralph H. Hruban, Charles J. Yeo, Scott E. Kern

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)27-32
Number of pages6
JournalNature genetics
Volume8
Issue number1
DOIs
StatePublished - Sep 1994

ASJC Scopus subject areas

  • Genetics

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