Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma
| Autor: | Charles J. Yeo, Ralph H. Hruban, Scott E. Kern, A. B. Seymour, Mieke Schutte, Stephan A. Hahn, Carlos Caldas, Mark Redston, L T da Costa, C. L. Weinstein |
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| Rok vydání: | 1994 |
| Předmět: |
Pancreatic disease
Molecular Sequence Data Biology Adenocarcinoma medicine.disease_cause Loss of heterozygosity Genetics medicine Tumor Cells Cultured Missense mutation Humans Gene Cyclin-Dependent Kinase Inhibitor p16 Mutation Base Sequence Point mutation medicine.disease Genes p53 Pancreatic Neoplasms medicine.anatomical_structure Cancer research Chromosome Deletion Pancreas Carrier Proteins Chromosomes Human Pair 9 Gene Deletion |
| Zdroj: | Nature genetics. 8(1) |
| ISSN: | 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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