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Medline ® Abstract for Reference 23

of 'Molecular pathogenesis of exocrine pancreatic cancer'

23
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Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.
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Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE
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Nat Genet. 1994;8(1):27.
 
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.
AD
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
PMID