Mutational analysis of the P16-binding domain of cyclin-dependent kinase 4 in tumors in the head region of the pancreas.
Alterations in genes involved in cell cycle regulation are common in many tumor types. In pancreatic adenocarcinomas, inactivating mutations in the CDKN2 gene, encoding the cyclin-dependent kinase inhibitor p16, are frequently observed. CDKN2 mutations have also been identified in the germline of 50% of patients with hereditary melanoma. Interestingly, such patients also have an increased risk for pancreatic cancers. In melanoma-prone kindreds with CDKN2 wild-type status, a mutation in one of the targets of p16, cyclin-dependent kinase 4 (CDK4) was reported, which abolishes p16 inhibition. To test the possible involvement of CDK4 mutations in pancreatic carcinoma, we analyzed sequence alterations in the p16-binding domain of CDK4 in DNA isolated from 32 tumors in the head region of the pancreas. Alterations in the CDK4 region between codon 1 and codon 56 were not observed in any of the tumors. Our results do not support disruption of the p16 pathway through CDK4 mutation as an oncogenic mechanism in pancreatic head tumorigenesis.
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
H M
HM
Ceha
M J
MJ
Clement
M M
MM
Polak
G J
GJ
Offerhaus
R J
RJ
Slebos
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014670:Ampulla of Vater / Q000473:pathology; D003138:Common Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins
D017931:DNA Primers; D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases