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

C Caldas, SA Hahn, LT da Costa, MS Redston… - Nature …, 1994 - nature.com
C Caldas, SA Hahn, LT da Costa, MS Redston, M Schutte, AB Seymour, CL Weinstein…
Nature genetics, 1994nature.com
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 …
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.
nature.com